Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We used molecular biology techniques to study the genetic events associated with the development of human esophageal cancer. Point mutations of the p53 tumor suppressor gene were detected in one of 10 squamous cell and one of 14 adenocarcinomas of the esophagus, a frequency that implicates this gene in tumorigenesis. However, the finding of p53 mutations in Barrett's epithelium adjacent to adenocarcinomas may have clinical implications for p53 as a premalignant marker for esophageal cancer.
J Thorac Cardiovasc Surg 1991 Nov
PMID:Oncogene activation in esophageal cancer. 194 88

Immunohistochemical detection of the p53 gene product by monoclonal antibodies has been shown to be associated with a poor clinical outcome in carcinomas of the breast and stomach. Because the prognostic relevance of p53 immunostaining in lung cancer is still under debate, we studied the expression pattern and clinical significance of such staining in 73 patients with operable non-small-cell lung cancer. p53 expression was detected on frozen sections with the use of monoclonal antibody p1801, which recognizes both the wild-type and mutant gene product (alkaline phosphatase-anti-alkaline phosphatase method). A tumor was considered p53 positive if more than 1% of the tumor cells were stained. The p53 expression pattern was compared with clinicopathologic parameters, and analysis of follow-up, based on the data of 65 patients, was done by a log rank test (median observation time, 780 days). Nuclear p53 staining was detected in 33 of 73 non-small-cell lung cancers (45.2%). Comparison with clinicopathologic parameters demonstrated that the p53 protein was detected more frequently in younger patients (younger than 50 years, p = 0.014), whereas no correlation was found with sex, tumor differentiation, tumor histologic type, or TNM stage. Surprisingly, follow-up analysis revealed that p53 staining was associated with an increased rate of disease-free survival, especially in patients with early stage tumor disease (p = 0.004) and in male patients (p = 0.023). Counter to previous studies in other solid tumors, immunocytochemical detection of p53 expression does not predict a poor clinical outcome in non-small-cell lung cancer. In early-stage lung cancer it might be associated with an improved disease-free survival, which suggests that the majority of the detected protein inherits the wild-type tumor suppressor function.
J Thorac Cardiovasc Surg 1995 Jun
PMID:Immunohistochemical detection of P53 protein is not associated with a poor prognosis in non-small-cell lung cancer. 777 84

The development of human adenocarcinoma of the lung involves multiple genetic changes including activation of oncogenes and loss of tumor suppressor genes. Patients whose lung tumors contain K-ras oncogene mutation, accumulation of the protein product of the tumor suppressor gene p53, or erbB-2/neu oncoprotein overexpression have been shown to have a worse prognosis. We examined these three genetic indicators in 29 lung adenocarcinomas to determine whether these markers are present in the same tumors or if they represent molecular changes that define different subsets of patients. P53 nuclear protein accumulation and erbB-2/neu protein overexpression were determined by immunohistochemical analysis of cryostat sections of tumor specimens and corresponding normal lung tissue. K-ras mutations were detected by radiolabeled oligonucleotide probes, specific for the various twelfth codon mutations, hybridized to exon 1 of K-ras, which was amplified by the polymerase chain reaction. Increased nuclear accumulation of p53 protein was found in 11 adenocarcinomas (38%). All of the p53 positive tumors were found to show high level staining and homogeneous expression of erbB-2/neu protein. K-ras mutations were detected in seven tumors (24%), all of which overexpressed erbB-2/neu. The presence of a K-ras mutation did not correlate with p53 accumulation. In total, 93% of the tumors were found to overexpress erbB-2/neu, the highest being in one tumor with erbB-2/neu gene amplification. The presence of K-ras twelfth codon mutation was associated with increased cigarette smoking. In conclusion, erbB-2/neu overexpression is a common event in lung adenocarcinomas. Furthermore, the presence of K-ras mutation and p53 protein accumulation define separate groups of patients. The mechanisms by which these genetic alterations interact or adversely affect prognosis is unknown.
J Thorac Cardiovasc Surg 1994 Feb
PMID:Alterations of K-ras, p53, and erbB-2/neu in human lung adenocarcinomas. 790 43

Barrett's esophagus is a metaplastic condition with an unpredictable potential for neoplasia. Mutations of the tumor-suppressor gene p53 have been implicated in the evolution of some carcinomas. These mutations frequently result in intranuclear protein accumulation, which can be detected immunohistochemically. This study was undertaken to determine whether p53 immunoreactivity in Barrett's esophagus is a marker of neoplasia and, if so, when it occurs in the metaplasia-dysplasia-carcinoma sequence. Twenty-eight esophageal resection specimens were studied. Barrett's mucosa was present in each specimen, low-grade dysplasia in 27, high-grade dysplasia in 26, intramucosal cancer in 18, and submucosal cancer in 5. Immunohistochemical staining with the monoclonal antibody Pab1801 was used to detect the intranuclear protein product of mutated p53. No p53 immunoreactivity was seen in specimens of Barrett's mucosa or low-grade dysplasia. p53 immunoreactivity was found only in specimens of high-grade dysplasia, intramucosal cancer, and submucosal cancer. Sixty-nine percent (18/26) of these specimens exhibited mutated p53; 18 of 26 specimens of high-grade dysplasia (69%), 12 of 18 intramucosal cancer specimens (67%), and two of five submucosal cancer specimens (40%) expressed mutated p53. When p53 staining was observed, the spectrum of neoplastic changes (high-grade dysplasia, intramucosal cancer, submucosal cancer) within the specimen was positive. We conclude that (1) p53 immunoreactivity in Barrett's esophagus is a frequent, but not inclusive, marker for high-grade dysplasia, intramucosal cancer, and submucosal cancer and (2) immunoreactivity occurs late in the metaplasia-dysplasia-carcinoma sequence, during the transition to high-grade dysplasia.
J Thorac Cardiovasc Surg 1994 Dec
PMID:p53 immunoreactivity in Barrett's metaplasia, dysplasia, and carcinoma. 798 83

Squamous cell carcinoma of the esophagus has an uneven geographic distribution with a strong prevalence in the South Carolina Lowcountry. Although many environmental influences and some genetic factors have been implicated in its development, the molecular events required for tumorigenesis have not been defined. Point mutations in the p53 tumor suppressor gene are the most commonly noted genetic defect in human tumors. Our study shows that p53 point mutations occur more frequently in patients with esophageal cancer from this region than in patients from other areas of the world where the disease is prevalent.
J Thorac Cardiovasc Surg 1994 Jul
PMID:Prevalence of p53 mutations in patients with squamous cell carcinoma of the esophagus. 802 58

Mutations of the p53 tumor suppressor gene, whose encoded protein is one of the chief regulators of the cell cycle, are proving to be the most common genetic alteration in human cancer. Point mutations have been detected in numerous human solid tumors. The types of point mutations in the p53 gene vary considerably in different kinds of human cancers, suggesting that specific etiologic agents are responsible for typical kinds and sites of mutations in the p53 gene. This study reports the detection of two unusual p53 mutations in a series of patients with lung cancer. The first case showed a one-base pair deletion at the end of exon 8, which is rarely affected by mutations, leading to a frameshift involving the following intron 8, exon 9, and intron 9. The second case exhibited two point mutations in codon 273, both either localized in the same codon on one allele or each mutation localized on a different allele in codon 273. Interestingly, the two mutations can be attributed to different mechanisms of base substitution. This is the first report of this kind. Because of evidence that the nature and site of p53 mutations reflect not only the mutagens involved in tumorigenesis but also the capacity for malignant transformation, the characterization of mutations of the p53 gene may provide a basis for assessing further risk factors, as well as for estimating prognosis in patients with lung cancer.
J Thorac Cardiovasc Surg 1994 Apr
PMID:Carcinogen-specific mutations in the p53 tumor suppressor gene in lung cancer. 815 32

The medical records and histologic documents of 14 patients treated at our institution for a thymic carcinoid tumor were reviewed. There were 3 women and 11 men with an age range from 35 to 71 years. One patient had a multiple endocrine neoplasia syndrome; another had a neurofibromatosis. Twelve tumors were revealed by local symptoms and two were asymptomatic. One patient had Cushing's syndrome that appeared secondarily and was related to metastases. Tumors ranged from 6 to 20 cm and had the characteristic histologic appearance of atypical carcinoid tumor. Immunohistochemical evaluations were done. Tumors were positive for cytokeratin (92%), neuroendocrine markers (100%), and p53 oncoprotein (29%). S-100 protein antibody revealed numerous sustentacular cells in one case. Overall survival was 46% and 31% at 3 and 5 years, respectively. However, all patients died of the disease within 109 months as a result of local progression (n = 5), local relapse (n = 3), distant metastases (n = 8), or a combination of these reasons. Median survival was 71, 30, and 5 months for patients who had total resection (n = 4), partial resection (n = 5), or simple biopsy (n = 4), respectively (p = 0.023). In conclusion, thymic carcinoid tumors can be considered thymic neuroendocrine carcinomas because of their malignant behavior and histologic appearance of atypical carcinoid tumors. Complete surgical resection offers the best hope for long-term survival.
J Thorac Cardiovasc Surg 1996 Jan
PMID:Thymic neuroendocrine carcinoma (carcinoid): a clinicopathologic study of fourteen cases. 855 58

We had previously identified p53 mutations in Barrett's esophagus and therefore began a multiinstitutional study to determine their significance as a marker for malignancy. Ninety-eight patients from four institutions were studied. Forty-eight patients (37 men and 11 women, mean age 56.2 years) had Barrett's esophagus with metaplasia or dysplasia but no evidence of malignancy at a mean follow-up of 2.2 years. Barrett's esophagus was classified as metaplasia with no evidence of dysplasia in 32 patients, as low-grade dysplasia in 13, and as high-grade dysplasia in three. The other 50 patients (46 men and four women, mean age 60.2 years) had adenocarcinoma arising in Barrett's esophagus. Tissues from normal stomach or esophagus, tumor, and Barrett's esophagus were obtained for deoxyribonucleic acid analysis by endoscopic biopsy from patients with Barrett's esophagus or cancer or during operations on some patients with Barrett's cancer. Exons 5 through 9 of the p53 gene were studied for mutations by single-strand conformational polymorphism analysis after polymerase chain reaction amplification. Mutations detected by single-strand conformational polymorphism analysis were confirmed by deoxyribonucleic acid sequencing. None of the tissue samples from patients with Barrett's esophagus alone and no dysplasia or low-grade dysplasia had any p53 mutations, but one of the three patients with high-grade dysplasia and no evidence of invasive malignancy did have a p53 mutation. Of the 50 patients with Barrett's cancer, however, 23 (46%) had p53 mutations in Barrett's epithelium, tumors, or both. Twenty of these patients had p53 mutations in the tumor only (n = 16) or in both tumor and Barrett's epithelium (n = 4), suggesting that the mutation plays a direct role in carcinogenesis. Mutations in Barrett's epithelium were found in one patient in the group without malignancy and in seven patients with cancer (one with no dysplasia, two with low-grade dysplasia, and five with high-grade dysplasia). In three patients with cancer, mutations occurred only in Barrett's epithelium, suggesting that such mutations may also be a marker for genomic instability. Mutations were predominantly found in exons 5, 7, and 8, and transitions from guanine to adenine were the most frequent changes. Mutations of p53 are clearly involved in the pathogenesis of Barrett's cancer for a subset of patients (46%), and the fact that we could detect mutations in premalignant Barrett's epithelium supports the hypothesis that p53 mutations may be a useful marker for patients at increased risk for development of invasive cancer.
J Thorac Cardiovasc Surg 1996 Feb
PMID:Mutations of p53 in Barrett's esophagus and Barrett's cancer: a prospective study of ninety-eight cases. 858 5

When solitary pulmonary tumors are observed in patients with a history of cancer, differentiation between metastasis and primary lung cancer is crucial for appropriate therapy. Assuming that p53 mutations are conserved in metastases, mutation analysis of the p53 gene would be a valuable tool in differentiating metastases from primary carcinomas of the lung. In nine of 267 resected lung tumors, the origin of the lung tumor could not be defined histologically. Five patients had a history of colorectal carcinoma, one had a history of breast carcinoma, one had a history of soft-tissue carcinoma, and one had a history of head and neck carcinoma. One patient with a clear cell carcinoma of the lung had been surgically treated for both renal and thyroid cancer. Material from one patient with adenocarcinoma of the lung, histologically defined regional lymph nodes, and distant brain metastasis served as a control. We extracted deoxyribonucleic acid from the snap-frozen tissue of the unclassified lung tumors, from paraffin-embedded tissue of the previously removed primary cancers, and also from peripheral blood of the patients. Exons 2 to 11 of the p53 gene were amplified in separated polymerase chain reactions and directly sequenced. In all cases, the presence of germline mutations was excluded by analysis of peripheral blood deoxyribonucleic acid. The p53 mutation detected in the deoxyribonucleic acid of the lung tumor of the control patient proved to be conserved in the lymph nodes as well as in the brain metastasis. In two cases, the lung tumors exhibited a p53 mutation not present in the previously removed primary tumor and were therefore classified as new primary lung cancers. In five cases, the lung tumors proved to be metastases of the first tumor, exhibiting the identical p53 mutation. One of these lung tumor samples could be identified as a metastasis from the renal cancer, but the corresponding thyroid cancer material was different. For two cases, molecular analysis remained inconclusive. In one case, no p53 mutation could be found in the compared samples; in the other, no deoxyribonucleic acid could be extracted. Analysis of p53 mutations allowed exact classification in tumors for which standard methods failed to distinguish between metastasis or primary tumor. More than two thirds of lung tumors in patients with previous gastrointestinal carcinoma were revealed to be metastases, but second primary lung cancer could also be diagnosed. This diagnosis allowed correct surgical and adjuvant treatment of these patients.
J Thorac Cardiovasc Surg 1996 Apr
PMID:Molecular genetic differentiation between primary lung cancers and lung metastases of other tumors. 861 43

A more effective gene therapy strategy for lung cancer using sequential cisplatin administration and adenovirus-mediated p53 gene transfer was developed on the basis of our previous observation of enhanced expression of a reporter gene in malignant cells exposed to cisplatin before gene transfer. Transfer of the normal (wildtype) p53 gene into cisplatin-treated H1299 cells, in which p53 is homozygously deleted, resulted in up to a 60% further inhibition of cell proliferation in vitro than p53 transfer into untreated H1299 cells. The cisplatin plus p53 gene transfer strategy yielded significantly greater apoptosis and tumor growth suppression in an animal model of subcutaneous H1299 tumor nodules than wildtype p53 gene transfer alone. The timing of cisplatin administration and p53 gene transfer was shown to be critical: cisplatin administration simultaneous with or subsequent to p53 gene transfer was less effective than cisplatin-first sequential treatment. Moreover, the in vivo inhibition of tumor growth was maintained by repeated cycles of treatment. This gene therapy strategy has been incorporated into a phase I clinical trial for the treatment of lung cancer and provides a basis for the development of improved therapeutic protocols.
J Thorac Cardiovasc Surg 1996 Nov
PMID:Gene therapy for lung cancer: enhancement of tumor suppression by a combination of sequential systemic cisplatin and adenovirus-mediated p53 gene transfer. 891 37


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