Abstract:
:Information suggests that the cyclooxygenase (COX) metabolites, the prostanoids, play a role in gall bladder physiology and disease. Non-steroidal anti-inflammatory drugs which inhibit COX enzymes have been shown in vivo and in vitro to alter the growth patterns of intestinal epithelial cells, and specific COX-2 inhibitors have been shown to decrease mitogenesis in intestinal epithelial cells. The present study was intended to evaluate the effect of specific COX inhibitors on the growth patterns of gall bladder cancer cells. Employing a human gall bladder cancer cell line, mitogenesis, apoptosis and prostaglandin E(2) (PGE(2)) formation were evaluated in response to serum and hepatocyte growth factor and transforming growth factor alpha stimulation in the presence and absence of specific COX-1 and -2 inhibitors. The effect of the mitogens on COX enzyme expression was also evaluated. Serum and the growth factors increased COX enzyme expression and mitogenesis, and decreased apoptosis as evaluated by the percentage of cells that were floating in culture media rather than attached. There was more DNA degradation in floating than in attached cells. The specific COX-2 inhibitor, but not the COX-1 inhibitor, decreased mitogenesis and increased gall bladder cell apoptosis as evaluated by the number of floating versus attached cells and the number of floating cells in the terminal phase of apoptosis or dead. The inhibition of mitogenesis and the increased apoptosis produced by the COX-2 inhibitor was associated with decreased PGE(2) production. The inhibition of replication of gall bladder cancer cells and the increase in apoptosis produced by the selective COX-2 inhibitor suggests that the COX enzymes and the prostanoids may play a role in the development of gall bladder cancer and that the COX-2 inhibitors may have a therapeutic role in the prevention of gall bladder neoplasms.
journal_name
Carcinogenesisjournal_title
Carcinogenesisauthors
Grossman EM,Longo WE,Panesar N,Mazuski JE,Kaminski DLkeywords:
subject
Has Abstractpub_date
2000-07-01 00:00:00pages
1403-9issue
7eissn
0143-3334issn
1460-2180journal_volume
21pub_type
杂志文章相关文献
CARCINOGENESIS文献大全abstract::Species differences in the metabolism of toxic chemicals can confound the extrapolation of experimentally determined risk data to man. However, it is often difficult to obtain reliable information on human metabolism, particularly of genotoxic agents. In this study, comparisons of chromatographic profiles of DNA adduc...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/7.6.965
更新日期:1986-06-01 00:00:00
abstract::To test the hypothesis that polymorphic variants of antioxidant genes modify the risk of pancreatic cancer, we examined seven single-nucleotide polymorphisms (SNPs) of genes coding for superoxide dismutase (SOD) 2, glutathione S-transferase alpha 4 (GSTA4), catalase and glutathione peroxidase in 575 patients with panc...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgp310
更新日期:2010-04-01 00:00:00
abstract::Diallyl disulfide (DADS), a sulfur compound from garlic has been shown to exert many biological effects: induction of carcinogen detoxication, inhibition of tumor cell proliferation, etc. These effects are consistent with its anticarcinogenic properties in animal models and could account for garlic protective effects ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgg182
更新日期:2004-01-01 00:00:00
abstract::We have shown previously that the difference between C57BL/6J and C3H/HeJ male mice in their susceptibilities to chemically-induced liver tumors results predominantly from an allelic difference at the Hepatocarcinogen sensitivity (Hcs) locus. This locus modulates the rate of growth of preneoplastic liver lesions and m...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/11.4.589
更新日期:1990-04-01 00:00:00
abstract::4-Aminobiphenyl (4-ABP), a potent carcinogen in rodents (liver cancer) and human (bladder cancer), is found as an environmental contaminant and in tobacco smoke. Hemoglobin adducts and lung DNA adducts of 4-ABP are found in tobacco smokers. In vitro metabolism studies with human and rat liver microsomes have shown tha...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/20.9.1825
更新日期:1999-09-01 00:00:00
abstract::Heat treatment of foods containing reducing sugars and amino acids during cooking or sterilization triggers a sequence of non-enzymatic reactions collectively known as the Maillard reaction. 5-Hydroxymethylfurfural (HMF), one of the major intermediate products in the Maillard reaction, has been found to possess cytoto...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/15.10.2375
更新日期:1994-10-01 00:00:00
abstract::Losses of heterozygosity (LOH) of the short arm of chromosome 19 are frequent in lung cancer, suggesting that one or more tumor suppressor genes are present in this region. The LKB1 gene, also called STK11, is somatically inactivated through point mutations and large deletions in lung tumors, demonstrating that LKB1 i...
journal_title:Carcinogenesis
pub_type: 杂志文章,评审
doi:10.1093/carcin/bgp035
更新日期:2009-04-01 00:00:00
abstract::We have measured the levels of thymine glycol (TG) and thymidine glycol (dTG) in human urine, using an HPLC method. The results show that all 30 specimens examined (including 10 non-neoplastic and 20 neoplastic human urines) contained significant amounts of TG and dTG, average levels (mean +/- SEM) were 0.376 +/- 0.02...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/14.7.1359
更新日期:1993-07-01 00:00:00
abstract::Barrett's esophagus (BE) and esophageal adenocarcinoma (ADC) is associated with reflux of duodenal contents. Cyclooxygenase (COX)-2 is over-expressed in BE and ADC, and supposedly contributes to esophageal carcinogenesis. The aim of this study is to investigate what effect a COX-2 inhibitor has on esophageal adenocarc...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgh340
更新日期:2005-03-01 00:00:00
abstract::High intake of red meat is associated with an increased risk of colon cancer. It has been suggested that fat from red meat is responsible, because high fat intake increases the concentration of cytotoxic lipids in the colon. Experimental studies have not unequivocally supported such a role for fat, however. Recently, ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/21.10.1909
更新日期:2000-10-01 00:00:00
abstract::Previous studies from our laboratory demonstrated that diallyl disulfide (DADS), an oil-soluble allyl sulfur compound found in processed garlic, markedly suppressed p34(cdc2) kinase activity and induced a G(2)/M phase arrest in cultured human colon tumor (HCT-15) cells. The present studies reveal that suppression of p...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:
更新日期:2000-06-01 00:00:00
abstract::The role of parity before and after N-methyl-N-nitrosourea (MNU) treatment in protection against mammary carcinogenesis was investigated. The effect of lactation on reduction in the incidence of mammary carcinoma was also examined. Parous rats were compared with respective age-matched virgins (AMVs). Pregnancy and lac...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/20.4.623
更新日期:1999-04-01 00:00:00
abstract::A hallmark of cancer is aberrant DNA methylation, consisting of global hypomethylation and regional hypermethylation of tumor suppressor genes. DNA methyltransferase inhibitors have been recognized as promising candidate anticancer drugs. Drug development has focused on DNA methylation inhibitors with the goal of acti...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgq221
更新日期:2011-02-01 00:00:00
abstract::A monoclonal antibody specific for cyclobutane thymine dimers in DNA was used in immunofluorescence studies to detect these lesions in skin sections taken from hairless mice that had been irradiated with UV-B. The dimer-specific fluorescence in epidermal cell nuclei was quantified with fluorescence microscopy through ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/12.5.861
更新日期:1991-05-01 00:00:00
abstract::Precursor T-cell lymphoblastic neoplasms are aggressive malignancies in need for more effective and specific therapeutic treatments. A significant fraction of these neoplasms harbor deletions on the locus 9p21, targeting the tumor suppressor CDKN2A but also deleting the aconitase 1 (ACO1) gene, a neighboring housekeep...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgz185
更新日期:2020-08-12 00:00:00
abstract::Reprogrammed metabolism has been identified as an emerging hallmark in cancer cells. It has been demonstrated that fructose-1, 6-bisphosphatase 1 (FBP1) as a rate-limiting enzyme in gluconeogenesis plays critical roles in tumor initiation and progression in several cancer types. However, function of FBP1 in hepatocell...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgw109
更新日期:2017-02-01 00:00:00
abstract::The role of sulfation in the metabolic activation of the liver carcinogen N-hydroxy-4'-fluoro-4-acetylaminobiphenyl (N-OH-FAABP) in male rat liver was investigated. N-OH-FAABP was a substrate for sulfotransferases in vitro and sulfation was inhibited by the sulfotransferase inhibitors pentachlorophenol (PCP) and 2,6-d...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/10.12.2285
更新日期:1989-12-01 00:00:00
abstract::Cytochrome P450 1B1 (CYP1B1) is an enzyme that has a unique tumor-specific pattern of expression and is capable of bioactivating a wide range of carcinogenic compounds. We have reported previously that coordinated upregulation of CYP1B1 by inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and the aryl hy...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgu190
更新日期:2014-11-01 00:00:00
abstract::To study the relationship between epidermal DNA synthesis and carcinogenesis, hairless mice of both sexes were given a single topical application of 1 mg N-methyl-N-nitrosourea (MNU) in acetone. A control group received only MNU, whereas other groups were injected i.p. with 5 mg hydroxyurea (HU), 1 h, 45 min and 15 mi...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/3.8.891
更新日期:1982-01-01 00:00:00
abstract::The effect of oral vitamin C supplementation on intragastric ascorbate levels and gastric mucosal DNA damage as measured by the 32P-postlabelling assay was assessed in 43 patients. In patients with normal gastric mucosa, treatment with vitamin C resulted in elevation of intragastric ascorbate levels in all cases. In t...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/15.2.291
更新日期:1994-02-01 00:00:00
abstract::An increased neuroendocrine (NE) cell population in prostate cancer is associated with more aggressive disease and recurrence after androgen-deprivation therapy, although the mechanism responsible is unknown. In this study, we report that the treatment of LNCaP cells with epidermal growth factor (EGF) in the presence ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgs139
更新日期:2012-06-01 00:00:00
abstract::The mutagen sensitivity assay is an in vitro measure of DNA repair capacity used to evaluate intrinsic susceptibility for cancer. The high heritability of mutagen sensitivity to different mutagens validates the use of this phenotype to predict cancer susceptibility. However, genetic determinants of mutagen sensitivity...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgn121
更新日期:2008-07-01 00:00:00
abstract::An in vivo method for assessment of DNA adduct formation and unscheduled DNA synthesis (UDS) in the esophagus of rats was devised. Small ventral incisions were made in the neck and upper abdomen regions of 6 week old F344 rats and ligation of the esophagus with thread at the two extreme ends performed to make an esoph...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/11.2.235
更新日期:1990-02-01 00:00:00
abstract::Chemical carcinogens are generally activated enzymatically to electrophiles that form covalently bound carcinogen-DNA adducts. Detoxifying enzymes are competing with the activating enzymes for these procarcinogenic chemical substrates. Wide person-to-person variations in these two types of enzymatic activities are fou...
journal_title:Carcinogenesis
pub_type: 杂志文章,评审
doi:10.1093/carcin/10.9.1563
更新日期:1989-09-01 00:00:00
abstract::Human fibroblasts repair DNA damaged by bleomycin through both short-patch and long-patch pathways, mediated by an aphidicolin-resistant (beta) and aphidicolin-sensitive (delta) DNA polymerase respectively (DiGiuseppe, J.A. and Dresler, S.L. (1989) Biochemistry, 28, 9515-9520). Despite certain similarities, aphidicoli...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/11.6.1021
更新日期:1990-06-01 00:00:00
abstract::Alkylation of DNA and hemoglobin was compared in male F344 rats given a single s.c. injection of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), or its major metabolite formed by carbonyl reduction, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL). In hepatic DNA, levels of 7...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/9.9.1665
更新日期:1988-09-01 00:00:00
abstract::A diet deficient in choline when fed to rats for as few as 3 days resulted in liver DNA damage. The damage could be monitored as alkali-labile lesions using alkaline-sucrose gradients as well as alkaline elution technique. The DNA damage disappeared when the choline-deficient diet was replaced by a choline-supplemente...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/7.10.1677
更新日期:1986-10-01 00:00:00
abstract::The in vivo formation of specific 7,12-dimethylbenz[a]-anthracene (DMBA)-DNA adducts in the mammary gland of the female Sprague-Dawley rat was studied in response to dietary butylated hydroxytoluene (BHT). Dietary BHT concentrations of 0.4 and 0.8% significantly inhibited total DMBA-DNA binding by 41.5 and 35.6% respe...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/12.10.1967
更新日期:1991-10-01 00:00:00
abstract::An intrasanguineous host-mediated assay was used to establish the mutagenic potential of a series of dialkylnitrosamines to E. coli K12/343/113 in the liver and spleen of mice. For calibrating purposes, dose- and time-dependent kinetics of mutation induction by the model compound diethylnitrosamine in this assay was d...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/2.9.909
更新日期:1981-01-01 00:00:00
abstract::O(6)-alkylguanine-DNA alkyltransferase (AGT) is a suicide protein that corrects DNA damage by alkylating agents and may also serve to activate environmental carcinogens. We expressed human wild-type and two active mutant AGTs in bacteria that lack endogenous AGT and are also defective in nucleotide excision repair, to...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/20.11.2089
更新日期:1999-11-01 00:00:00