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

The prognostic value of cell nuclear DNA content, S-phase fraction and p53 protein accumulation in esophageal squamous-cell carcinomas was studied in a consecutive series of 80 patients from a high-incidence region of southern Thailand, who underwent esophagectomy between 1983 and 1993. Flow cytometry was used to determine tumor ploidy, DNA index and S-phase fraction, while p53 protein accumulation was evaluated immunohistochemically using the monoclonal anti-p53 antibody, CO7. Biomarkers were correlated with clinico-pathologic findings and survival by univariate and multivariate analysis. p53 protein was found in 40 tumors (50%), and was associated with significantly reduced overall survival. In patients with immunopositive tumors, depth of primary tumor invasion, lymph-node status. TNM stage and tumor grade were also significant prognostic factors. Additional predictors of reduced overall survival after esophagectomy, determined by flow cytometry, included S-phase fraction above 10%, aneuploidy (DNA index 1.2-1.8) and multiploidy (DNA index > 2.2). This study further implicates p53 in the pathogenesis of esophageal squamous-cell carcinoma. Prognostic factors such as p53 protein, S-phase fraction and DNA index may be useful in stratifying patients for adjuvant therapies in future clinical trials of esophageal cancer.
 ...
PMID:Prognostic value of DNA index, S-phase fraction and p53 protein accumulation after surgical resection of esophageal squamous-cell carcinomas in Thailand. 759 Dec 36

DNA ploidy pattern analyzed by cytofluorometry and p53 protein expression using immunohistochemical method were studied in 35 cases of esophageal cancer. p53 protein were positive in 19 cases (54%), and DNA aneuploidy pattern were detected in 26 cases (74%). There was no relationship between DNA ploidy pattern or p53 expression and clinico-pathological factors. DNA aneuploidy or p53 positive cases were significantly poor prognoses in five-year survival rate. DNA aneuploidy and p53 positive cases were worst in four groups. It is effective for evaluation of biological malignancy and detection of post operative schedules to study not only clinico-pathological factors but also DNA ploidy pattern and p53 expression in esophageal cancer.
 ...
PMID:[Analysis of p53 expression and DNA ploidy pattern in esophageal cancer]. 761 71

Results of epidemiological studies have shown that nitrosamine-induced carcinogensis is involved in esophageal cancer in China. In order to demonstrate the mechanism at molecular level, Multiple tumor suppressor genes Rb, p53, APC and MCC in human fetus esophageal epithelium treated with NMBzA (in vitro) for 24 hours or three weeks and esophageal carcinoma induced by NMBzA were analyzed with PCR amplification and direct sequencing. In PCR amplification analysis. Rb, p53, APC and MCC deletions in esophageal carcinoma of human fetus induced by NMBzA were found, but no deletions of these genes was demonstrated in NMBzA-treated human fetal esophageal epithelium. PCR direct sequencing analysis revealed mutation of p53, Rb and MCC genes in human fetal esophageal epithelium treated with NMBzA for three weeks. The results first confirmed (in vitro) that nitrosamine can cause mutations and deletions of multiple tumor suppressor genes in human esophageal epithelium. The mutations of tumor suppressor genes in nitrosamine-induced esophageal carcinoma may occur in the early stage, while deletions in late stage of carcinogenesis.
 ...
PMID:[Multiple tumor suppressor genes in esophageal carcinoma induced in human fetus esophageal epithelium by NMBzA]. 765 18

Resistance to chemotherapy remains a serious problem in the successful treatment of gastric and esophageal cancers. DNA-damaging agents alter levels of p53 protein in several cell types and it has been speculated that regulation of p53 can be involved in the resistance or sensitivity of cancer cells to some chemotherapeutic drugs, depending on whether cells have mutant or wild-type p53; however, little is known about the relationship of p53 to drug sensitivity in gastric/esophageal cancers. Here we have examined human gastric/esophageal adenocarcinoma cell lines for p53 mutational status, chemosensitivity to 5-fluorouracil, mitomycin C, and cis-dichlorodiammineplatinum(II), alteration in p53 levels following exposure of cells to these drugs, and the mechanisms involved in regulating p53 levels. Our results indicate that wild-type p53 protein levels increase after treatment with each of these drugs via either post-translational and/or translational mechanisms and that this increase in wild-type p53 appears to be required for effective chemotherapeutic growth control of gastric/esophageal adenocarcinoma cells. In contrast, gastric/esophageal cancer cells expressing either mutated p53 protein or no p53 protein are more resistant to the growth-inhibitory effects of these drugs, despite the fact that drug exposure can also increase mutant p53 levels by a translational mechanism. Thus, these data indicate that the mutational status of p53 is predictive of chemosensitivity of gastric and esophageal adenocarcinomas, and suggest a mechanism in which p53 protein contributes to the cellular response to chemotherapy.
 ...
PMID:The mutational status of p53 protein in gastric and esophageal adenocarcinoma cell lines predicts sensitivity to chemotherapeutic agents. 766 47

The p53 tumor suppressor gene has recently been implicated in the pathogenesis of human esophageal cancer. To assess potential clinical applications for this molecular marker, 52 patients with primary esophageal adenocarcinoma were studied prospectively. p53 protein accumulation was evaluated immunohistochemically in surgically resected esophageal tissues, and correlated with clinicopathologic findings and survival. All patients underwent total esophagectomy with reconstruction, completely resecting all gross disease. Immunopositivity was seen in 28 of 52 (54%) primary adenocarcinomas, and was associated with a trend towards reduced postoperative survival (P = 0.06; log-rank). Regional lymph node metastases were found in 30 (58%) patients. Thirteen of 30 (43%) regional lymph node metastases were immunopositive, which was the most significant predictor of overall survival by univariate (P = 0.02; log-rank) and multivariate analysis (P = 0.05; Cox regression). This study further implicates p53 in esophageal tumor development and progression. The immunohistochemical finding of p53 protein in primary esophageal adenocarcinomas and regional lymph node metastases appears to be associated with reduced overall survival for this disease. If these preliminary observations are confirmed in larger prospective studies, p53 may prove to be a clinically useful molecular marker in future clinical trials of esophageal cancer.
 ...
PMID:Prognostic value of p53 protein in esophageal adenocarcinoma. 766 67

Epidemiological investigation showed that N-methylbenzylnitrosamine (NMBzA) has been associated with increased incidence of esophageal cancer (EC) in Linxian county, a high incidence area. In present study, our results indicate that NMBzA can induce amplification and over-expression of EGFr gene in human fetal esophageal epithelium (HFE) treated with NMBzA for 24 hours as shown by southern blot assay and immunohistochemistry. The papillary hyperplasia was induced in HFEs that cultured with NMBzA for 1 to 3 weeks. Amplification of c-myc and int-2 gene in HFEs treated by NMBzA for 1 week and 3 weeks was found, respectively. Deletions of p53 and Rb gene were found in human fetal esophageal carcinomas induced by NMBzA. Overexpression of p53 protein in human fetal esophageal carcinomas detected by immunohistochemical methods indicates that p53 gene mutation(s) may be occured. The HFE explants treated in vitro with NMBzA for 3 weeks were inoculated subcutanously into balb/c nude mice. No tumor was found in 5 months after inoculation, suggesting that only changes of oncogene(s) are insufficient to induce full transformation. Other genetic alterations (such as functional inactivation of Rb or/and p53 tumor suppressor genes) may be necessary in the further progression of malignant lesions.
 ...
PMID:[Alterations of oncogenes in human fetal esophageal epithelium induced by N-methylbenzylnitrosamine (NMBzA)]. 772 Apr 92

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.
 ...
PMID:[Effect of NMBzA on the oncogene and multiple tumor suppressor genes in monkey esophageal epithelium]. 778 Nov 21

We investigated clonal intratumor heterogeneity by comparing different areas of each tumor in 20 gastrointestinal cancers from female patients (1 esophageal cancer, 5 stomach cancers, and 14 colorectal cancers). In all 19 cases informative for X-inactivation analysis with the M27 beta and/or the phosphoglycerate kinase probes, the tumors were clonal. Separate areas from a given tumor showed identical X-inactivation patterns, providing evidence for its single-cell origin. Of 20 cancers, 11 showed p53 gene mutations (base pair insertions, point mutations, and one case of a base pair deletion) in exons 5-8. A particular p53 gene mutation was identical in all tumor areas investigated per case. The minisatellite probes detected loss of heterozygosity or new mutant alleles at 1p33, 1q21, 5q35, 17p13, or 18q21. In seven cases mutations at particular loci were restricted to one or two areas per tumor, while in another seven cases they were common to all tumor areas. Loss of heterozygosity or new alleles detected at the microsatellite loci D2S123, D3S1611, D5S107, D17S261, or D18S34 [(CA)n repeats] were common to all tumor areas in 7 of 19 cases. In another seven cases, however, microsatellite mutations at these loci were restricted to one to three areas per tumor. Tracing clonal intratumor heterogeneity would permit one to study the hierarchy of mutational events in cancers where no premalignant lesions can be harvested. Most important, our study indicates that clonal intratumor heterogeneity might lead to sampling errors in the molecular diagnosis of cancer biopsy specimens when using mini- or microsatellite markers.
 ...
PMID:Somatic mutations detected by mini- and microsatellite DNA markers reveal clonal intratumor heterogeneity in gastrointestinal cancers. 779 14

Gastrointestinal cancers involve genetic alterations in multiple oncogenes, multiple tumor suppressor genes, and multiple DNA repair genes. However, common and different genetic changes are observed in esophageal, gastric, and colorectal carcinomas, respectively. Inactivation of the p53 gene and expression of CD44 abnormal transcripts are common events that serve as a powerful tool for cancer diagnosis. Gene amplification of cyclin D is found preferentially in esophageal cancer, whereas gene amplification of cyclin E and c-met is frequently associated with gastric cancer. Mutations of the cyclin-dependent kinase inhibitor genes also occur in esophageal and gastric cancers. However, the scenario of multiple gene changes differs depending on the two histologic types of gastric cancer, because they may have different genetic pathways. Interestingly, the frequency of genetic instability is also quite different between the two types of gastric cancer. A new strategy of molecular diagnosis for gastrointestinal cancers, which started as routine work at Hiroshima City Medical Association Clinical Laboratory last August, may provide a new approach to cancer diagnosis for the next decade.
 ...
PMID:Genetic alterations in human gastrointestinal cancers. The application to molecular diagnosis. 788 67

p53 gene in human esophageal cancer (EC) and cancer of gastric cardia was analyzed. Southern blotting hybridization revealed that five of 35 of EC sample were found to contain abnormal structure of p53 gene, including 2 deletions and 3 rearrangements; two of 27 adjacent non-tumor tissues also contain abnormal structure of p53 gene (7.4%), among them one case was fragment deletion and another case was rearrangement. PCR-direct sequencing technique was used to detect p53 point mutation within exon and intron 5 through 9. Fifteen of 30(50%) of esophageal squamous cell carcinomas contained mutation of p53 gene. Five of 11(45%) adjacent non-tumor tissues also contained mutation of p53 gene. An esophageal adenocarcinoma showed p53 mutation. Three of 4 carcinoma of gastric cardia showed p53 mutation. Mutation spectrum in EC: 8 of 22 cases (36.4%) of p53 mutation were G:C to A: T transition, 6 of 22 cases (27.3%) of p53 mutation were frameshift mutation, including 13.6% (3/22) insertion and 9.1% (2/22) deletion mutation. Some new sites of p53 mutation in human EC were identified. The results suggest that the p53 gene plays an important role in carcinogenesis of human esophagus and gastric cardia.
 ...
PMID:[Mutation of p53 gene in human cancers of the esophagus and gastric cardia]. 795 92


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>