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)

p53 is one of the most important tumor suppressor genes. Mutation of the p53 gene can be detected immunohistochemically as over-expression of its protein in the nucleus. The p53 gene product is known to regulate cell growth and proliferation. Genetic alterations related to the carcinogenesis or progression of esophageal cancer are poorly understood. We examined accumulation of p53 protein in esophageal squamous cell carcinomas including early-stage cancers, and its clinicopathological significance. p53 immunoreactivity in the cancer tissues was found in 61 (79.2%) of 77 esophageal squamous cell carcinomas. Over-expression of p53 protein (diffusely and focally positive staining) was seen in 70.1% (54/77). p53 over-expression was detected not only in the cases of in situ or intramucosal carcinomas, but also in invasive carcinomas. No significant correlations were found between p53 over-expression and clinicopathological features such as depth of tumor invasion, lymph node metastasis or venous/lymphatic invasion. These results suggested that p53 mutations may be closely associated with the early-stage of pre-invasive esophageal carcinoma, and p53 gene mutations may play an important role in the carcinogenesis of human esophageal cancer.
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PMID:Accumulation of p53 in esophageal squamous cell carcinoma. 1156 72

In view of the significance of MDM2 as a regulator as well as critical target of wild type p53, this study was undertaken to determine the alteration in MDM2 expression in esophageal squamons cell carcinoma (ESCC) and its relationship to clinicopathological parameters as well as p53gene and protein status. Immunohistochemical analysis of MDM2 and p53 proteins on paraffin embedded sections from 64 surgically resected ESCCs and matched histologically normal tissues showed overexpression of MDM2 protein in 23/64 (36%) ESCCs, while the histopathologically normal esophageal tissues did not show detectable level of MDM2 immunoreactivity. Interestingly, MDM2 /p53 + phenotype was observed in 37/64 (58%) cases. None of the cases with p53 mis-sense mutations (12/30, 40%) showed detectable level of MDM2 protein. Missense p53 mutations were significantly associated with discordant p53 + /MDM2 immunophenotype (p= 0.004). The most intriguing feature of the study was accumulation of MDM2 in the absence of detectable p53 in 11% of and overexpression of MDM2 and p53 in 25% of ESCCs, suggesting a p53-independent role for MDM2 in a subset of tumors. These results underscore the involvement of MDM2 in p53-dependent and -independent pathways in the pathogenesis of esophageal cancer in the Indian population.
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PMID:Alterations in MDM2 expression in esophageal squamous cell carcinoma: relationship with p53 status. 1169 47

As the primary metabolite of alcohol, acetaldehyde (AA) may be responsible for many pathological effects related to consumption of alcohol, such as esophageal cancer. The spectrum of p53 mutations in esophageal tumors is indicative of the involvement of exogenous agents, such as tobacco smoke. There is, however, no experimental proof for the involvement of alcohol as data on mutational spectrum induced by AA in human genes is completely lacking. The aim of this study is to investigate whether AA leaves mutational fingerprint in the HPRT reporter gene in human peripheral T cells. Pre-existing in vivo HPRT mutants were removed from PHA-stimulated T lymphocytes before in vitro treatment with 2.4 mM AA for 24 h. Following cell growth to allow mutation expression, independent 6-thioguanine-resistant mutants were selected from large numbers of subcultures showing a 3-fold induction of mutant frequency on average. A total of 73 induced and 36 spontaneous mutants were found to carry a missense, nonsense, frameshift or splice mutation. Base substitutions were identified in the coding or splicing sequences of 55 induced and 26 control mutants. The induced base changes were mainly G > A transition (40%, G on non-transcribed strand) followed by A > T transversions (14.5%, A on non-transcribed strand). The control mutants had significantly (P = 0.04) less G > A transition (15.4%) and completely lacked A > T transversions. We also identified 5'-AGG-3' or 5'-AAG-3' as potential target sequences for AA-induced G > A transitions. This specific mutational spectrum induced by AA is consistent with the known formation and persistency of N(2)-ethyl-2'-guanosine adduct and with the predominance of G > A transitions and mutations at A:T base pairs in the p53 gene of esophageal tumors. We conclude that AA may be involved in the pathogenesis of esophageal cancer.
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PMID:Mutational spectrum induced by acetaldehyde in the HPRT gene of human T lymphocytes resembles that in the p53 gene of esophageal cancers. 1169 45

We studied whether the immunohistochemical status of dihydropyrimidine dehydrogenase (DPD) and p53 can be used to predict the sensitivity to chemoradiotherapy (CRT) in patients with esophageal cancer. In 19 patients who did not undergo preoperative CRT, the immunoreactivity of DPD and p53 in biopsied specimens correlated well with those in surgically resected specimens (DPD: 100%, p53: 73%). Fifteen patients were treated with 5-FU (250-300 mg/body/day: day 1-5, 8-12), low-dose cisplatin (10 mg/body/day: day 1, 8) and radiotherapy (30-40 Gy). The response rate (CR + PR) for CRT in these patients was 40%. All tumors that showed CR or PR demonstrated low expression of DPD. However, all tumors with high DPD expression showed MR or NC. However, the expression of p53 did not correlate with the response rate for CRT. Therefore, the effect of CRT for esophageal cancer may be predicted by immunohistochemical examination of DPD in biopsied tumor specimens.
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PMID:[Immunohistochemical study of dihydropyrimidine dehydrogenase (DPD) and p53 in biopsied specimens of esophageal cancer before chemoradiotherapy]. 1170 71

Gastroesophageal reflux disease (GERD) and columnar-lined esophagus with intestinal metaplasia (Barrett's esophagus) are the major recognized risk factors for adenocarcinoma of the esophagus. The American College of Gastroenterology recommends that patients with long-standing GERD symptoms (particularly those 50 years of age or older) undergo endoscopic screening to identify Barrett's esophagus and that those patients who have Barrett's esophagus undergo regular endoscopic surveillance. These recommendations are made with the expectation that screening and surveillance will decrease mortality from esophageal cancer, although this association is unclear. Nonetheless, retrospective studies have shown that endoscopic surveillance can detect some early, curable neoplasms in patients with Barrett's esophagus. Dysplasia in Barrett's esophagus is widely regarded as the precursor of invasive malignancy. Although grading dysplastic changes is largely subjective, dysplasia remains the most appropriate biomarker for clinical evaluation of Barrett's esophagus. Flow-cytometric and p53 abnormalities may be earlier and more specific markers for cancer development, but application of these abnormalities is not yet recommended for clinical practice. Endoscopic surveillance also is adversely affected by biopsy sampling error. Techniques that may minimize biopsy sampling error include chromoendoscopy, endosonography, optical coherence tomography, and fluorescence detection techniques. Further studies are needed to clearly define the role of these techniques in surveillance, and none is practical for routine clinical use at this time. Although not specifically recommended, experimental ablative therapies, such as photodynamic therapy, can be considered by physicians for their patients with high-grade dysplasia in Barrett's esophagus, if they are provided as part of an established, approved research protocol.
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PMID:Screening and surveillance for complications related to gastroesophageal reflux disease. 1174 38

AIM:To investigate the risk factors of esophageal cancer (EC) in urban areas of Xi'an and to determine the association between overexpression of P53 and these risk factors.METHODS: All cases (89) and controls (97) were permanent residents in urban areas of Xi'an, all cases of primary EC had been histologically confirmed, controls were inpatients with non-cancer and nonsmoking-related disease. Cancer tissues and tissues adjacent to the cancer of 65 cases and 24 available normal esophageal tissues of controls were detected for P53 overexpression by the immunohistochemical method.RESULTS: The smoking and familial history of cancer were significantly associated with EC in Xi'an inhabitants. The laboratory assay indicated that P53 positive stain in EC was 50.0%(34/65)and 6.1%(4/65) in tissues adjacent to the cancer, but no positive stain was found in normal esophageal tissues of controls. The results showed that P53 overexpression in EC was closely related to smoking and cases with familial history of cancer.CONCLUSION: Smoking and familial cancer history were important risk factors for EC,and the alteration of P53 gene may be due to smoking and inheritance factors.
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PMID:Overexpression of P53 and its risk factors in esophageal cancer in urban areas of Xi'an. 1181 33

AIM:To determine the extent of apoptosis and its possible relationship with the changes of p53, Waflp21, bcl-2, and c-myc at different stages of esophageal carcinogenesis.METHODS:Two hundred and forty-one esophageal biopsy samples from symptom-free subjects and 38 surgically resected esophageal carcinoma tissues from a high-risk population for esophageal cancer in Henan, China were used in this study.Apoptotic cells and apoptotic bodies were identified by well-established morphological criteria. The extent of apoptosis and its possible relationship with the rate of cell proliferation (PCNA) and changes of p53, Waf1p21, bcl-2,and c-myc were analyzed in samples with esophageal precancerous and cancerous lesions.RESULTS:The apoptotic cells, identified morphologically, were located in the same proliferative compartment of hyperproliferative cell population in the esophageal epithelia as the cells immunostaining-positive for p53, bcl-2, c-myc and PCNA.The apoptotic indices (total number of apoptotic cells and apoptotic bodies per mm(2) of the tissue section) were low in the normal epithelia,and increased significantly as the lesions progressed from BCH to DYS and to SCC.The extent of apoptosis correlated well with the cell proliferation indices based on PCNA. The total number of positive cells for p53 stain was much higher than that of apoptotic cells. No difference in apoptotic indices was found between p53-positive and p53-negative samples. Waf1p21-positive cells resided in cell layers were higher in number than p53 and PCNA-positive cells. The number of immunostaining positive cells for Waflp21 increased slightly from normal to BCH,but decreased in DYS and SCC. Positive staining samples for bcl-2 and c-myc increased as the lesions progressed from BCH to DYS and to SCC. No apparent correlation between apoptosis and Waf1p21, bcl-2 or c-myc expression was observed.CONCLUSION:The extent of apoptosis was low in normal esophageal epithelium and increased as the lesions progressed. The apoptotic cells were located in the same hyperproliferative cell compartment as cells immunostaining-positive for p53, bcl-2,c-myc and PCNA,but no apparent correlation between apoptosis and these parameters was observed,possibly due to the complexities of molecular changes in esophageal carcinogenesis.
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PMID:Apoptosis and its relationship with cell proliferation, p53, Waf1p21, bcl-2 and c-myc in esophageal carcinogenesis studied with a high-risk population in northern China. 1181 1

The multiple occurrence of squamous cell carcinoma is frequent in the upper aerodigestive tract (UADT). Risk factors not only for esophageal cancer, but also for multiple cancer in the UADT, were reviewed. Both cigarettes smoking and alcohol drinking are will known risk factors for esophageal cancer. The joint effect of these 2 factors on the occurrence of esophageal cancer is considered to be synergetic, but familial aggregation of esophageal cancer is also reported. Regarding the multiple occurrence of cancer of the UADT, both heavy smoking and heavy drinking play an important role. In addition, our studies revealed that a family history of UADT cancer might also be a risk factor for multiple cancer. Recent improvement of molecular biology techniques have helped to show that tumor-suppressor genes, such as p53 and FHIT, may be candidates for target genes of these risk factors.
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PMID:Risk factors for esophageal cancer and the multiple occurrence of carcinoma in the upper aerodigestive tract. 1182 80

The aminothiol WR1065, the active metabolite of the cytoprotector amifostine, exerts its antimutagenic effects through free-radical scavenging and other unknown mechanisms. In an earlier report, we showed that WR1065 activates wild-type p53 in MCF-7 cells, leading to p53-dependent arrest in the G(1) phase of the cell cycle. To determine whether WR1065 activates p53 by modulating protein conformation, we analyzed its effects on p53 conformation and activity in the esophageal cancer cell line TE-1. This cell line contains a mutation in codon 272 of p53 (p53(V272M), with methionine instead of a valine), conferring temperature-sensitive properties to the p53 protein. At the nonpermissive temperature (37 degrees C), p53(V272M) adopts the mutant p53 conformation (nonreactive with the antibody PAb1620), does not bind specifically to DNA, and is not activated in response to DNA-damaging treatment. However, treatment with 0.5-4 mM WR1065 partially restored wild-type conformation at 37 degrees C, stimulated DNA binding activity, and increased the expression of p53 target genes WAF-1, GADD45, and MDM2, leading to cell-cycle arrest in G(1). These results suggest that WR1065 activates p53 through a mechanism distinct from DNA-damage signaling, which involves modulation of p53 protein conformation.
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PMID:Restoration of wild-type conformation and activity of a temperature-sensitive mutant of p53 (p53(V272M)) by the cytoprotective aminothiol WR1065 in the esophageal cancer cell line TE-1. 1187 Aug 84

Esophageal cancer is a highly malignant disease in which progression is observed in most patients even at the first medical examination. Neoadjuvant cytoreduction treatments are frequently used for the purpose of tumor down-staging, increasing the resection rate, and possibly improving survival. Although combination therapy with radiation and anticancer agents is available, no satisfactory treatment regimen has yet been established due to the development of resistance. Based on the concepts of genetic alteration in carcinogenesis, cancer gene therapy has been developing rapidly. We previously reported the growth inhibitory effect of adenovirus-mediated wild-type p53 gene transfer into esophageal squamous carcinoma cell lines. After extensive preclinical study of p53 gene therapy in vitro and in vivo, we are conducting a phase I/II clinical trial. The target of this trial is patients with unresectable esophageal cancer resistant to chemoradiotherapy. As of December 1, 2001, 8 candidates had been admitted to our hospital. After extensive examination, 4 patients were enrolled in this trial. After giving informed consent, the first patient received injections of Ad5 CMV-p53 on December 19, 2000. No serious adverse events have occurred so far in these patients, and the trial has been conducted safely.
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PMID:[Gene therapy for esophageal cancer]. 1199 27


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