Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0546837 (esophageal cancer)
 8,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In an attempt to further characterize non-irradiated contact-inhibited confluent monolayer of BALB/c 3T3 cells (= Contact-Sensitive Plates; CSP) as substrata for in vitro drug sensitivity testing, we compared the efficiency of colony formation with panels of cell lines on CSP with that on plastic dishes or in agar. Tumorigenicity in athymic nude mice was also examined. We found that: (1) HeLa cells, 2 esophageal cancer lines, rat 3Y1 fibroblasts transformed by either adenovirus type 12, mouse polyoma virus, Rous avian sarcoma virus, or plasmid DNA carrying v-Ha-ras oncogene all formed colonies on CSP and in agar and at the same time was tumorigenic. The efficiency of colony formation on CSP proved always to be higher than that in agar. (2) None of the 4 "normal" fibroplastic cell lines formed colonies on CSP or in agar and were tumorigenic. (3) Simian virus 40 and adenovirus E1A gene transformed rat 3Y1 fibroblasts formed colonies on CSP but not in agar, and were not tumorigenic. Therefore, CSP was found to provide selective and efficient growth of neoplastic cells when compared to other substrata and is also helpful in detecting incompletely transformed cells.
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PMID:Confluent BALB/c 3T3 cells monolayer provides selective and efficient growth of neoplastic cells. 237 37

Epidemiological studies have demonstrated a strong association between human esophageal cancer and exposure to N-nitroso carcinogens. Esophageal tumors can be induced in experimental animals, especially in rats, by many N-nitroso carcinogens. In the present study, rat esophageal tumors induced by methylbenzylnitrosamine (MBNA) and MBNA-transformed esophageal cell lines were analyzed for activated protooncogenes. DNAs from four Fisher 344 rat esophageal papillomas were examined for their ability to induce morphological transformation of NIH 3T3 cells. One of four esophageal tumors was positive in this assay. Southern blot analysis of this NIH 3T3 transformant revealed that the transforming gene was an activated Ha-ras gene. The activating mutation in the Ha-ras gene was identified by amplifying and then sequencing the first exon of this gene. A GC----AT transition at the second base in codon 12 of the Ha-ras gene was detected. The tumor DNAs from the transfection-negative samples were also amplified, and sequencing analysis of the first exon revealed a GC----AT transition in codon 12. In addition, 14 formalin-fixed and paraffin-embedded rat esophageal papillomas were shown to contain the same mutation in one of the alleles of the Ha-ras gene. In contrast, no point mutation was found in codons 12, 13, and 61 of the Ha-, Ki-, or N-ras genes in MBNA-transformed rat esophageal cell lines. The GC----AT transition detected in the esophageal tumors by DNA sequencing was confirmed by slot blot oligonucleotide hybridization of the polymerase chain reaction-amplified DNAs. The fact that mutated Ha-ras genes were detected in the esophageal papillomas suggests that activation of this gene occurred early in the process of neoplastic progression. The point mutation detected in the Ha-ras gene appears to result from a direct genotoxic effect of MBNA involving formation of the O6-methylguanine adduct. Taken together, these studies suggest that the activation of the Ha-ras gene plays an important role in the induction of esophageal neoplasia in the Fisher 344 rat by MBNA.
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PMID:Mutational activation of the cellular Harvey ras oncogene in rat esophageal papillomas induced by methylbenzylnitrosamine. 240 14

Mutations of ras oncogene and multiple tumor suppressor genes p53, Rb and APC in esophageal epithelium of rhesus monkey fed with one dose of N-methyl-N-benzylnitrosamine (NMBzA 30mg/kg), which was found in high incidence areas of esophageal cancer in China, were analysed by PCR and direct sequencing. Mutation at codon 12 of Ha-ras gene was not found in esophageal epithelium of monkey fed with NMBzA. Some mutations of p53 gene were found in esophageal epithelium of monkey after being fed with NMBzA for 24-48 hours. Some mutation of Rb and APC were found in esophageal epithelium of monkey after being fed with NMBzA for 48 hours. The mutation fingerprints of these genes disappeared in esophageal epithelium of monkey after being fed with NMBzA for 5 days. The results demonstrated that chemical carcinogen NMBzA can induce mutations of multiple tumor suppressor genes in monkey (in vivo) and indicated that the alteration of tumor suppressor genes in the initial stage of carcinogenesis needs many hits by chemical carcinogen. These alterations of p53, Rb, APC genes were similar to the changes of these genes in some reported previously primary esophageal cancer.
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PMID:[Effect of NMBzA on the oncogene and multiple tumor suppressor genes in monkey esophageal epithelium]. 778 Nov 21

A rapid, simple, and nonradioactive method for diagnosing point mutations of c-K-ras oncogenes in gastroenterologic cancers is described. This method involved the selective amplification of DNA fragments from cancer tissues of surgical specimens with specific oligonucleotide primers, followed by digestion with restriction enzymes that recognized artificially created or naturally occurring restriction sites. To detect codon 12 mutations, an artificial Msp I site was created by introducing a single nucleotide mismatch into the 5' mutagenesis primer. Using a similar approach, an Hae III site was created to detect codon 13 mutations. Bal I and MBo II sites were used to detect codon 61 mutations. A total of 61 gastroenterologic cancer cases were studied. Of 35 cases of colorectal cancer, 7 showed mutations: 6 at codon 12 and 1 at codon 13. In 1 of 2 cases of cholangiocellular carcinoma, point mutation at codon 12 was found. One case of duodenal cancer showed point mutation at codon 12. No mutations were found in the cases of hepatocellular carcinoma (4), gastric cancer (12), esophageal cancer (3), or pancreatic cancer (2).
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PMID:Mutation analysis of K-ras oncogenes in gastroenterologic cancers by the amplified created restriction sites method. 824 18

More than 70 cell lines were established from esophageal cancer, including 15 TE-series cell lines established by the authors. This article reviews molecular and cellular features of esophageal cancer cells from studies using these cell lines as well as primary tumors. The subjects reviewed include primary cultures of normal epithelium of the esophagus and of esophageal tumors, their growth and differentiation properties, chromosomal aberrations, protein kinase C, growth factors and their receptors, oncogenes, and tumor-suppressor genes. Lesions of genetic loci in esophageal cancer include the absence of mutations in ras genes in primary tumors, amplification and overexpression of the c-erbB gene, co-amplification of hst-1 and int-2 genes, mutations, and allelic loss of tumor suppressor genes, p53, Rb, APC, and MCC. Future clinical improvement will be achieved on the basis of the understanding of molecular and cellular features of esophageal cancer cells.
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PMID:Molecular and cellular features of esophageal cancer cells. 850 34

Mutated ras genes have been found to be conspicuously absent from primary tumors of the esophagus, although high expression of ras p21 oncoprotein in some esophageal squamous cell carcinomas and mutations of the Ki- and Ha-ras genes in esophageal carcinoma cell lines have been reported. In this study, we found amplification of the Ki-ras gene in four of 10 esophageal adenocarcinomas (40%). No such amplification was observed among 61 squamous cell carcinomas, one pseudosarcomatous carcinoma, and eight esophageal cell lines, nor in six adenocarcinomas of the stomach. In two samples on which immunohistochemical analysis could be performed, we found overexpression of Ki-ras proteins when compared with normal samples. This Ki-ras amplification in esophageal tumors did not correlate with any pathological feature of the tumors, with the survival of the patients, or with the presence of other genetic alterations. These findings provide the first evidence for amplification of the Ki-ras gene in human esophageal cancer, which is restricted to adenocarcinomas. We also found that six of eight adenocarcinomas had point mutations in the p53 gene; this is a considerably higher prevalence than that reported for esophageal squamous cell carcinomas. These results strongly suggest that esophageal adenocarcinomas differ from squamous cell carcinomas in their molecular genetic characteristics.
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PMID:High frequency of Ki-ras amplification and p53 gene mutations in adenocarcinomas of the human esophagus. 851 18

Perillyl alcohol (POH) is a monoterpene found in lavender, spearmint, and cherries. Phase I clinical trials with this agent have shown a favorable toxicity profile and preliminary data indicate some chemotherapeutic efficacy in advanced cancers. Animal studies have demonstrated the ability of POH to inhibit tumorigenesis in the mammary gland, liver, and pancreas. Although the precise mechanism of action is unclear, POH has been shown to inhibit the farnesylation of small G-proteins, including Ras, up-regulate the mannose-6-phosphate receptor, and induce apoptosis. Previous studies in our laboratory using the rat model of squamous cell carcinoma of the esophagus have shown that a specific Ha-ras codon 12 mutation is important for tumor promotion and progression. Given the limited toxicity of POH in humans, its proven efficacy in several animal models and its potential to inhibit Ha-ras farnesylation, we conducted an animal study to evaluate the efficacy of POH as a chemopreventive agent for squamous cell carcinoma of the esophagus. Male Fischer-344 rats were treated s.c. with 0.25 mg/kg b.w. of N-nitrosomethylbenzylamine three times a week for 5 weeks. Three days after the final carcinogen dose, they were started either on control diet or diets containing 0.5 or 1.0% POH. At 25 weeks, the animals were sacrificed, and esophageal tumors were counted. Animals fed either dose of POH showed a significant increase in dysplasia when compared with controls (P < 0.05) and a nonsignificant trend toward increased tumor multiplicity. Additionally, 1.0% POH did not affect Ras membrane localization. These data indicate that POH has a weakly promoting effect early in nitrosamine-induced esophageal tumorigenesis and suggest that POH may not be an effective chemopreventive agent for esophageal cancer in humans.
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PMID:Perillyl alcohol as a chemopreventive agent in N-nitrosomethylbenzylamine-induced rat esophageal tumorigenesis. 1275 Feb 58

The Ras/Raf/MEK/ERK (MAPK) signal transduction cascade is an important mediator of a number of cellular fates including growth, survival and apoptosis. The aim of this study was to determine the incidence of B-raf, Kirsten-ras (K-ras) and Neuroblastoma-ras (N-ras) gene mutations in esophageal squamous cell carcinoma (ESCC) in the Greek population. DNA was extracted from 30 ESCC and 32 normal esophageal specimens and screened for V600E B-raf, and K-ras/N-ras codon 12 mutations, by PCR-RFLP based analysis. Among the genes tested, only the heterozygous K-ras mutation was detected in 5 out of the 30 ESCC specimens (16%), whereas no mutation was found in the normal esophageal tissue (P < 0.022). The normal samples were screened negative for N-ras and V600E B-raf mutations. The increased risk of esophageal cancer was correlated with tobacco use (OR = 3.5, P < 0.023) and alcohol abuse (OR = 7.22, P < 0.001), accompanied with the high incidence of the k-ras codon 12 mutation (22%, OR = 1.77 and 21%, OR = 1.52), respectively. A similar positive association was seen in human papilloma virus (HPV)-infected patients (OR = 5.66, P < 0.003). Our overall findings demonstrate that the mutational activation of the K-ras gene, HPV infection and tobacco or alcohol abuse, can be considered independently or in combination as high risk factors for ESCC development.
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PMID:K-ras mutation, HPV infection and smoking or alcohol abuse positively correlate with esophageal squamous carcinoma. 1859 5

To reveal the molecular mechanism of the growth-inhibitory effects of high concentrations of EGF, accumulations of p53 protein and p21ras expression in MX-1 and UM-1 breast cancer and ES-4 esophageal cancer transplanted into nude mice were investigated after local injections of 2 mug of EGF or 2 mug of TGF-beta. The accumulation of p53 protein and expression of p21ras were determined by using the methods of Western immunoblotting and p53 mutant selective quantitative ELISA assay. p53 mutation was investigated by using the PCR analysis and DNA sequencing. Contents of intra-cellular-cAMP of these tumors were also determined by radioimmunoassay. Results showed that the high concentration of EGF induced the accumulations not only of wild type p53 protein, but also of mutant p53 protein in these tumors growth-inhibited by EGF. In ES-4 esophageal cancer, 2 mug of EGF induced the up-regulation of p53 and the down-regulation of p21ras. On the contrary, 2 mug of TGF-beta induced the down-regulation of p53 and the up-regulation of p21ras in UM-1 human breast cancer. The point mutation of p53 gene was found at codon 181 contained C to T transversions (Amino acid switch: Arg --> Cys) in ES-4 esophageal cancer. The accumulations of p53 proteins were also associated with the down regulated intra-cellular-cAMP induced by high concentrations of EGF. These results indicate that p53 gene and ras gene are involved in the signal pathway of EGF and that the p53 gene may have some important role as a negative growth factor by suppressing ras oncogene in the mechanism of tumor growth inhibition through the high concentration of EGF.
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PMID:P53 tumor-suppressor gene and cyclic adenosine-monophosphate in breast and esophageal cancer are regulated through high-concentration of epidermal growth-factor. 2157 46

BACKGROUND This study was designed to explore the correlations of promoter methylation in Wnt inhibitory factor-1 (WIF-1), ras-association domain family member 1A (RASSF1A), and Cadherin 13 (CDH13) genes with the risk and prognosis of esophageal cancer (EC). MATERIAL AND METHODS A total of 71 EC tissues from resection and 35 adjacent normal tissues were collected. Methylation status in the promoter region was detected by methylation- and non-methylation-specific primers. Corresponding mRNA levels were detected by reverse transcriptase-polymerase chain reaction (RT-PCR). Correlations between the methylations of these 3 genes and clinicopathologic characteristics were analyzed. Kaplan-Meier method and Cox regression model were used to investigate the relationships between WIF-1, RASSF1A, and CDH13 promoter methylations and the prognosis of EC. RESULTS Compared with adjacent normal tissues, the methylation frequencies of WIF-1, RASSF1A, and CDH13 genes were significantly higher but the mRNA levels of these 3 genes were significantly lower in EC tissues (all P<0.05). WIF-1 and CDH13 promoter methylations were associated with the degree of tumor differentiation and WIF-1 and RASSF1A promoter methylations were associated with age (all P<0.05). The survival rates of patients with WIF-1, RASSF1A, and CDH13 methylations were significantly lower than those of patients without methylation (all P<0.05). WIF-1, RASSF1A, and CDH13 promoter methylations were independent risk factors affecting the prognosis of EC (all P<0.05). CONCLUSIONS WIF-1, RASSF1A, and CDH13 promoter methylations are associated with EC. The methylation levels are negatively related with the prognosis in EC.
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PMID:Correlations of Promoter Methylation in WIF-1, RASSF1A, and CDH13 Genes with the Risk and Prognosis of Esophageal Cancer. 2750 57


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