Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fifteen primary non-small-cell lung carcinomas (8 adenocarcinomas and 7 squamous-cell carcinomas) were analyzed by multiparameter flow cytometry for their expression of p53 and c-myc proteins. In addition, the fraction of cells staining with the proliferation-associated antibody Ki-67 and DNA ploidy was determined. These 4 biological markers were analyzed in parallel samples from a single-cell suspension made from fresh, frozen biopsies. Thus, the internal relationship between these markers within each tumor-cell population was established. Three different anti-p53 antibodies were used: PAb 421, PAb 1801 and PAb 240. All 15 tumors were p53-positive with the antibodies PAb 1801 and PAb 240, whereas only 9 were positive as judged by the antibody PAb 421. This indicates that the choice of p53 antibody is not irrelevant. Ten tumors were c-myc-positive; 7 of these were adenocarcinomas. The c-myc-positive tumors had a significantly higher level of p53 expression, judged by PAb 1801 and PAb 240, than c-myc-negative tumors. For PAb 421, there was no difference. We did not find any correlation between Ki-67 staining and expression of p53 and c-myc proteins, either with DNA ploidy, S-phase fraction or histological type. Our study indicates that there might be an association between accumulation of p53 protein and c-myc over-expression in non-small-cell lung cancer, and that this in particular might apply to adenocarcinomas. Furthermore, we show that multiparameter flow cytometry is a powerful tool in the study of the relationship between different markers in a cell population.
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PMID:Quantitation of biological tumor markers (p53, c-myc, Ki-67 and DNA ploidy) by multiparameter flow cytometry in non-small-cell lung cancer. 133 53

Radon increases the risk of lung cancer in smoking and non-smoking underground miners. To investigate the mutational spectrum associated with exposure to high levels of radon, we sequenced exons 5-9 of the p53 tumour suppressor gene and codons 12-13 of the Ki-ras protooncogene in 19 lung cancers from uranium miners exposed to radon and tobacco smoke. Mutations were not found in Ki-ras, but 9 p53 mutations, including 2 deletions, were found in 7 patients by direct DNA sequencing after polymerase chain reaction amplification of DNA from formalin-fixed, paraffin-embedded tissue. In tumours from 5 patients, the mutation produced an aminoacid change and an increased nuclear content of p53 protein. The tumours with either a stop codon or frame-shift deletion in the p53 gene were negative by immunohistochemistry. None of the mutations were G:C to T:A transversions in the coding strand of the p53 gene, which are the most frequent base substitutions associated with tobacco smoking, and none were found at the hotspot codons described in lung cancer. The observed differences from the usual lung cancer mutational spectrum may reflect the genotoxic effects of radon.
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PMID:Mutations of p53 and ras genes in radon-associated lung cancer from uranium miners. 134 94

The reverse transcription-polymerase chain reaction-single strand conformation polymorphism (RT-PCR-SSCP) analysis and sequencing were used to examine p53 gene alterations in 18 surgical specimens of primary lung cancers obtained in Japan. Somatic mutations resulting in amino acid changes were found in eight of the 18 cases (44%). Seven missense mutations were located in amino acid-conserved domains or their vicinities (codons 110 to 307). Most mutations were found at G-C pairs, suggesting that specific carcinogens are involved in the etiology of lung cancer. The p53 mutations showed a significant association with a history of smoking (P = 0.0294). We suggest that the p53 mutations may be associated with smoking-induced lung carcinogenesis.
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PMID:Mutations in the P53 tumour suppressor gene in primary lung cancer in Japan. 134 31

Squamous cell carcinomas of the head and neck (SCCHN) are associated strongly with the use of tobacco and alcohol, but little is known about the molecular pathogenesis of these tumors. In the present study, we analyzed SCCHN for mutations in the tumor suppressor gene p53 by immunocytochemistry and complementary DNA sequencing. Overexpression of p53 protein was detected in 13 (100%) of 13 SCCHN cell lines and in tumor cells cultured directly from 10 (77%) of 13 patients with SCCHN. Direct evidence for p53 mutations was obtained by sequencing p53 complementary DNA from eight SCCHN cell lines and two tumor xenografts. The genetic alterations included seven missense mutations resulting in single amino acid substitutions, a mutation encoding a stop codon, one 10-base pair deletion, and one 2-base pair addition. All seven missense mutations were G to T transversions, five of which were clustered at codons 245 and 248. A similar high frequency of G to T transversions predominates in lung cancer, another tobacco-related disease. Mutation of the p53 gene is the most common genetic alteration detected in SCCHN and implicates this gene locus as a critical site of specific damage by mutagenic carcinogens in tobacco, one of the important risk factors in the etiology of this disease.
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PMID:Frequent p53 mutations in head and neck cancer. 139 25

Cytogenetic and p53 mutation analysis in two cases of severe dysplasia of the bronchial epithelium in lung cancer patients and p53 immunostaining in a third one are reported. The finding of both chromosomal deletions of 17p and p53 mutation indicates that these changes may take place early in the process of lung carcinogenesis.
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PMID:Deletions of 17p and p53 mutations in preneoplastic lesions of the lung. 139 34

Bronchial epithelial dysplasia is believed to precede invasive squamous cell carcinoma of the lung. Six paired dysplasia and tumour samples were distinguished histologically in sections of formalin-fixed paraffin-embedded lung tissue from patients with lung cancer. Additionally, samples of dysplastic bronchial epithelium were obtained from patients without lung tumours. Microdissection of the unstained sections provided dysplastic and tumour samples from which DNA was prepared for comparison with the patients' constitutional genotype, using polymerase chain reaction-based restriction fragment length polymorphism analysis. All six samples of tumour and the paired adjacent samples of bronchial dysplasia showed loss of heterozygosity (LOH) at loci on the short arm of chromosome 3. Five of the six cases showed involvement of the p53 gene as assessed by LOH at the AccII site within the gene, and by immunoreactivity to CM-1, an antibody which recognizes the mutated form of the p53 protein in paraffin-embedded material. Of the dysplastic samples, obtained from patients without invasive tumours, all three showed LOH at 3p; one sample showed LOH at the AccII polymorphic locus within the p53 gene, and another sample, uninformative at this locus, stained positively with this antibody. These results indicate that somatic genetic changes are present in preinvasive lesions in the bronchus.
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PMID:p53 and chromosome 3 abnormalities, characteristic of malignant lung tumours, are detectable in preinvasive lesions of the bronchus. 140 39

Advances in the understanding of the process of carcinogenesis may allow prevention, diagnosis, and treatment of cancer to be approached at the molecular level. Studies in our laboratory show that growth factors (transforming growth factor alpha), dominant oncogenes (HER-2/erb B2 and K-ras), and tumor suppressor genes (p53) are functionally important in the maintenance of the malignant phenotype of human non-small-cell lung cancer cells. Application of these findings to clinical problems include the identification of p53 mutations as markers for malignant change in Barrett's epithelium, the use of discordant p53 mutations to diagnose second primary malignant neoplasms in patients with head and neck cancer, and the potential for therapy by the reversal of genetic lesions.
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PMID:Molecular surgery for cancer. 144 90

This study was undertaken to analyze the effect of wild-type p53 transfection on the growth potential of a human lung cancer cell line Hut292DM expressing endogenous wild-type p53. Transfection efficiencies obtained with either the wild-type or a mutant p53 complementary DNA revealed a significant decrease in the number of colonies obtained with the wild-type p53 as compared to the mutant p53 complementary DNA (27%) or control vector DNA only (20%), suggesting that wild-type p53 inhibited the growth of Hut292DM cells. A series of wild-type and mutant p53 transfection clones were then analyzed for the presence and expression of the exogenous p53 gene. Polymerase chain reaction amplification revealed that 98% of mutant p53 transfection clones analyzed contained the exogenous p53 gene as opposed to 47% for wild-type p53 clones. The majority of mutant p53 clones expressed high levels of exogenous p53 mRNA and protein as analyzed by Northern and Western blots, respectively. In contrast, all wild-type p53 clones analyzed failed to express exogenous p53 mRNA transcript or protein of a normal size. Aberrant-size p53 mRNA was detected in two wild-type p53 clones (X833.W2 and W18), and Western blot analysis revealed that these clones expressed truncated p53 proteins (M(r) 45,000 and 33,000 respectively). No difference in proliferation rates in vitro or in tumorigenic potential in nude mice were observed between mutant p53 clones or control cell lines. In contrast, a wild-type p53 clone (X833.W2) exhibited a significantly reduced tumorigenic potential in nude mice, whereas its in vitro proliferation rate was comparable to parental Hut292DM cells. The data indicate that exogenous expression of wild-type p53 is incompatible with Hut292DM lung cancer cell proliferation in vitro and suggest that p53-mediated growth control in vitro and in vivo may be dissociated and exerted by separate domains of the p53 protein.
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PMID:Growth suppression mediated by transfection of p53 in Hut292DM human lung cancer cells expressing endogenous wild-type p53 protein. 145 87

Proto-oncogenes (H-ras-1 and L-myc) and tumor-suppressor gene (p53) loci have been implicated in lung carcinogenesis. DNA restriction fragment length polymorphisms at these gene loci are being evaluated in a case-control study as markers predictive of risk for cancer or of prognosis when cancer is present. The cases and controls had a cigarette-smoking history of 40 or more pack years or other abnormalities in pulmonary function tests, their ages were closely matched (64 years for cases and 61 years for controls) and the ratio of Caucasians to African Americans was close to unity (cases, 0.95:1.00, controls, 1.00:0.88). The H-ras-1 gene contains an insertion deletion polymorphism. Inheritance of rare H-ras-1 alleles, defined by MspI digestion, confers a relative risk for lung cancer of 2.0 (95% confidence interval, 0.5-7.3) for Caucasians and 3.2 (0.9-11.6) for African Americans (74 cases, 67 controls). The L-myc gene sequence has a restriction site (EcoR1) polymorphism between the second and third exons. Inheritance of restriction site-present alleles was reported to confer poor prognosis (presence of lymph node metastases) in Japanese lung cancer patients. This hypothesis was tested in both case-control study subjects (56 cases, 55 controls) and additional surgical cases (40), but no evidence was found to support the hypothesis in the U.S. population. The p53 gene is a tumor-suppressor gene that can encode either a proline or an arginine in the 72nd residue. No associations was found between the minor allele (proline) and diagnosis of lung cancer (76 cases, 68 controls).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Relationship of H-ras-1, L-myc, and p53 polymorphisms with lung cancer risk and prognosis. 148 64

Since the nuclear accumulation of p53 protein is known to correspond well with mutation of the p53 tumor suppressor gene, the authors examined 88 primary lung cancer specimens immunohistochemically using anti-p53 mouse monoclonal antibody, pAb1801, and analyzed the relationship between the immunohistochemical results and clinicopathological features. Nuclear localization of p53 protein was found in 43/88 (49%) tumor specimens, but not in the corresponding normal lung tissues. The percentage of cases showing nuclear p53 localization varied according to the histological type. In squamous cell carcinoma, nuclear p53 localization was found in 15/26 (57%), appearing more frequently than in other histologic types. However, no obvious correlation was observed between nuclear p53 localization and patients' age, sex, history of smoking, TNM factor, degree of differentiation, or any other clinicopathological features analyzed. In adenocarcinoma, nuclear p53 localization was found in 20/46 (43%). Incidence of positive cases was significantly correlated with regional lymph node metastasis, distant metastasis, and pathological stage (P less than 0.05). These results indicate that mutation of the p53 tumor suppressor gene plays an important role in the development of primary lung cancer, and that nuclear accumulation of p53 protein is a potential prognostic factor in adenocarcinoma of the lung.
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PMID:Clinicopathological significance of nuclear accumulation of tumor suppressor gene p53 product in primary lung cancer. 154 66


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