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)

To better understand diseases of the thoracic space, pathologic findings of thoracoscopic open lung biopsy are described based on thoracoscopic anatomy and pleural mesothelioma. A positive colloidal iron stain in the plasma membrane of the mesothelial cells indicates the presence of hyaluronic acid, which appeared to decrease the friction between the lung and thoracic cavity. Excess fluid in the pleural cavity was removed from specific sites in the parietal pleura with stomas. We evaluated the pathologic features of 57 video-thoracoscopic open lung biopsies. Specific diagnoses were established in 89%, and of these half were pneumothorax. Nonspecific pathologic changes were found in 11%, of which interstitial pneumonia was the most common. This procedure is useful in taking a large number of specimens for diagnosis, and to evaluate the degree and progress of fibrosis. The differential diagnosis of mesothelioma from pulmonary adenocarcinoma, reactive mesothelial hyperplasia, and sarcoma of the pleura are described. Also, to understand mutations of the p53 tumor-suppressor gene in mesothelioma, mesothelial lesions were studied with immunostaining for p53 antibody (DO-7) and with in situ hybridization for p53 mRNA. In immunohistochemical staining for DO-7, all reactive mesothelial cells were positive, and 75% of mesotheliomas including epithelial, biphasic, and sarcomatous types were positive, and 75% of mesotheliomas including epithelial, biphasic, and sarcomatous types were positive. mRNA for p53 was expressed in all reactive mesothelial cells, and in 55% of allmesotheliomas.
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PMID:[Thoracoscopic anatomy, significance of pathologic findings in thoracoscopic open lung biopsy, and pleural mesothelioma]. 760 22

The p53 gene is well known as a tumour suppressor gene. In addition, the mutated p53 gene is detected in a variety of human cancers including lung cancer, and is considered as an oncogene. Lung cancer is also frequently associated with interstitial lung diseases. Therefore, it may be possible to hypothesize that there might be some abnormality of p53 gene in interstitial lung diseases. This work examined the relationship between the p53 protein and gene in lung tissues of 28 patients with interstitial lung diseases. Among 28 patients, 13 cases were pathologically diagnosed to have usual interstitial pneumonia (UIP), 12 cases were diagnosed as having collagen vascular lung diseases, and three cases were diagnosed to have a non-specific interstitial pneumonia. Twenty-three tissue samples were obtained by open lung biopsy and five samples were taken by autopsy. Paraffin-embedded tissues were treated by microwave, and stained with an anti-p53 antibody (DO7) by the Avidin-Biotin-Peroxidase (ABC) method. In selected patients, mutations in exons 5-8 of the p53 gene were also examined by single-strand conformation polymorphism (SSCP) analysis and DNA sequence. In addition, the presence of anti-p53 antibodies in patients' sera was screened for by ELISA. Fifteen samples (53.6%) revealed overexpression of the p53 protein in the nuclei of alveolar epithelial cells. However, SSCP or sequence analysis, which was performed in 13 tissues, showed no mutations in exons 5-8 of the p53 gene. In conclusion, p53 proteins were overexpressed in interstitial lung diseases, and the expressed p53 protein was considered to be wild-type. This wild-type p53 protein may play a role in blocking the transformation of proliferative epithelial cells.
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PMID:Overexpression of p53 protein in interstitial lung diseases. 961 10

Fas is expressed in various cells and transduces the cell death signal. p21 is a mediator of p53-dependent G1 arrest associated with deoxyribonucleic acid (DNA) damage. The upregulation of p53 and p21 associated with DNA damage in idiopathic pulmonary fibrosis has been described previously. In this study, p53, p21, and Fas expression and DNA damage were examined in interstitial pneumonia associated with collagen vascular diseases (CVD-IP). DNA damage was assessed by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick end-labelling (TUNEL) and p53, p21 and Fas proteins were detected by immunohistochemistry in 13 cases of CVD-IP, 13 of sarcoidosis, seven of hypersensitivity pneumonitis (HP) and eight control patients with normal lung parenchyma. TUNEL-positive signals were found in bronchiolar or alveolar epithelial cells in 11 of 13 (85%) specimens of CVD-IP, but not in sarcoidosis, HP or controls, except for a case of chronic HP with pulmonary fibrosis. p53, p21 and Fas were detected in bronchiolar or alveolar epithelial cells in nine (69%), 10 (77%) and 12 (92%) of 13 specimens of CVD-IP, respectively, but not in sarcoidosis, HP or controls, except for a case of chronic HP. These results suggest that the upregulation of p53, p21 and Fas in bronchiolar and alveolar epithelial cells associated with deoxyribonucleic acid damage may participate in the process of pulmonary fibrosis in interstitial pneumonia associated with collagen vascular diseases and chronic hypersensitivity pneumonitis.
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PMID:Expression of p53, p21 (Waf1/Cip1/Sdi1) and Fas antigen in collagen vascular and granulomatous lung diseases. 981 69

We report an 83-year-old man with pancreatic body cancer of 4.5 cm in diameter. Peripheral leukocyte count was 15,700/microl and the serum concentration of granulocyte-colony stimulating factor (G-CSF) was 123 pg/ml (normal, 6.0-21.9 pg/ml) on admission. Furthermore, not only K-ras codon 12 (GGT --> GAT) but also p53 at codon 247 (CGG --> CCG) mutations were identified in the pancreatic juice aspirated endoscopically. We performed chemotherapy with two courses of 5-fluorouracil, pirarubicin hydrochloride, and mitomycin-C, resulting in no beneficial effect. After the second course the patient developed interstitial pneumonia, probably caused by anticancer drugs, and died 4 months after the tumor was detected. In the autopsy tissue, the tumor macroscopically occupied the pancreas body and was 7 x 6 x 5 cm in size. Histopathologic diagnosis of the tumor was poorly differentiated adenosquamous carcinoma. Immunohistochemical staining of the autopsy tissue showed that pancreatic cancer cells were positive for G-CSF. This is the first case report of G-CSF-positive pancreatic cancer confirmed by immunohistochemistry.
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PMID:Pancreatic cancer associated with granulocyte-colony stimulating factor production confirmed by immunohistochemistry. 985 71

It has been reported that patients with pneumoconiosis occasionally have a diffuse interstitial fibrosis (DIF) that resembles interstitial pneumonia, but little is known about the relation between pneumoconiosis-associated DIF and the risk of lung cancer. In the present study, we evaluated the incidence of DIF by chest CT and its contribution to lung cancer in 563 patients with nonasbestos pneumoconiosis. Fifty-five (10%) of the 563 patients had DIF. Pneumoconiosis with DIF had an exceedingly high concurrence of lung cancers when compared with pneumoconiosis without DIF (29 [53%] of 55 versus 78 [15%] of 508, p < 0.001). Squamous cell carcinomas (SCCs) of the lung from pneumoconiosis with DIF exclusively comprised peripheral-types, as compared with SCCs from pneumoconiosis without DIF (13 [100%] of 13 versus 33 [72%] of 46, p = 0.03). In addition, lung cancers arose frequently from the area of DIF in pneumoconiosis with DIF (20 [74%] of 27). Furthermore, our pathologic examination revealed that dysplasias from pneumoconiosis with DIF were significantly more frequently observed in peripheral bronchioli than were dysplasias from pneumoconiosis without DIF (11 [69%] of 16 versus 20 [30%] of 66, p = 0.01). p53 expression evaluated by immunohistochemistry was frequently observed in dysplasias from pneumoconiosis with DIF, although it was not significantly different compared with that in dysplasias from pneumoconiosis without DIF (5 [50%] of 10 versus 12 [38%] of 32). Taken together, these results may suggest a positive causal relationship between pneumoconiosis and peripheral-type SCCs of the lung, and further indicate a pivotal role of diffuse fibrosis for the excess incidence of lung cancers, especially peripheral-type SCCs, in DIF-type pneumoconiosis.
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PMID:Pneumoconiosis-related lung cancers: preferential occurrence from diffuse interstitial fibrosis-type pneumoconiosis. 1090 57

Idiopathic pulmonary fibrosis (IPF) is a specific form of chronic interstitial pneumonia limited to the lung and characterized by a fibroproliferative response with only minor signs of inflammation, which almost always causes rapid fibrotic destruction of the lung. In this study, we investigated genomic instability in IPF, using microsatellite DNA analysis, aiming to detect any specific genetic alterations for this disease. We used 40 highly polymorphic microsatellite DNA markers, in multiplex PCR assays, to examine 52 sputum specimens from IPF patients versus correspondent venous blood. Loss of heterozygosity (LOH) was found in 20 (38.5%) patients in at least one locus. These alterations were found on markers previously associated with lung cancer located on 1p34.3, 3p21.32-p21.1, 5q32-q33.1, 9p21 and 17p13.1 where MYCL1, FHIT, SPARC, p16(Ink4) and TP53 genes have been mapped respectively. These data provide new insights into IPF pathogenesis and a new perspective for its correlation with lung cancer.
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PMID:MYCL1, FHIT, SPARC, p16(INK4) and TP53 genes associated to lung cancer in idiopathic pulmonary fibrosis. 1216 6

Seventy-two cases of idiopathic pulmonary fibrosis (IPF) were examined from 2856 consecutive autopsy cases at the Japanese Red Cross Medical Center in Tokyo from 1973-1996. Primary lung cancer had arisen in 31 of 72 cases of IPF (43%), significantly higher than the incidence in cases without IPF (8.1%) and in the cases with non-IPF chronic lung diseases (11.9%). Hyperplastic epithelial foci in the honeycomb lesions of IPF cases were significantly more prominent in the lower than in the upper lobe, in cases with or without lung cancer, and they were more prominent in the lower lobe of IPF with than in those without cancer. The length of hyperplastic epithelial foci in the lower lobe of IPF cases was longer than that in interstitial pneumonia-associated with collagen vascular diseases. There was a higher PCNA labeling index of hyperplastic epithelial foci in IPF cases than in cases of interstitial pneumonia-associated with collagen vascular diseases. The PCNA labeling index was almost the same between smokers and nonsmokers with IPF. Overexpression of p53 was observed in hyperplastic epithelial foci in honeycomb lesion of IPF. DNA ploidy analysis of hyperplastic epithelial foci in the paraffin sections of 12 IPF cases revealed aneuploidy patterns in eight cases. These results strongly suggest that accelerated cell proliferation occurs in the honeycomb lesion of IPF, and that regenerative epithelia becomes susceptible to carcinogenic agents in addition to the smoking effect.
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PMID:Hyperplastic epithelial foci in honeycomb lesions in idiopathic pulmonary fibrosis. 1224 24

Products of the p63 gene, a recently described member of the p53 family, are constitutively expressed in the basal cells of human bronchi and bronchioli. The truncated isoforms of the p63 gene (deltaN-p63 proteins) counteract the apoptotic and cell cycle inhibitory functions of p53 after DNA damage, and this property is likely to be central in the cell renewal strategy of stratified epithelial tissues. To investigate the dysfunctional repair processes that characterize idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP), we immunohistochemically analyzed the expression of the transactivating and dominant-negative isoforms of the p63 gene on 16 tissue samples obtained from patients suffering from this disorder. In most IPF cases herein investigated, epithelial cells expressing deltaN-p63 were observed at sites of abnormal proliferation at the bronchiolo-alveolar junctions, characterized by epithelial hyperplasia, squamous metaplasia, bronchiolization, and abnormal p53 nuclear accumulation. Similar features were not observed in normal lung and in samples taken from other pulmonary diseases used as controls, including acute interstitial pneumonia, idiopathic bronchiolitis obliterans organizing pneumonia, nonspecific interstitial pneumonia, and desquamative interstitial pneumonia. On the basis of these findings, we can hypothesize a new model for UIP pathogenesis, involving a deregulated development of mesenchymal-epithelial interactions and abnormal proliferation of epithelial cells at the bronchiolo-alveolar junction after cell injury. In our view, the progressive loss of alveolar tissue and lung remodeling after injury in IPF/UIP is concomitantly produced by pneumocyte loss and alveolar collapse on one hand and by progressive bronchiolar proliferation and architectural distortion on the other.
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PMID:Abnormal re-epithelialization and lung remodeling in idiopathic pulmonary fibrosis: the role of deltaN-p63. 1237 68

We previously demonstrated that the up-regulation of p53, Fas, and DNA damage are present in lung epithelial cells from patients with idiopathic interstitial pneumonias (IIP). Fas ligation induces apoptosis of lung epithelial cells predominantly through the direct activation of the caspase cascade via caspase-8 activation, whereas the up-regulation of p53 and other cellular stresses can induce mitochondria-mediated apoptosis. In this study, we investigated the incidence of mitochondria-mediated apoptosis of epithelial cells in IIP. We performed TUNEL staining to detect apoptotic cells and western blot analysis and immunohistochemistry to assess the expression and activation of caspases and the cytochrome c release from mitochondria in lung tissues from eight patients with usual interstitial pneumonia, five patients with nonspecific interstitial pneumonia, and eight patients with normal lung parenchyma. The expressions of pro- and cleaved caspase-8, 9, 3, and cytochrome c release from the mitochondria were all significantly increased in the lung tissues of IIP compared with normal lung parenchyma. The positive signals for caspases in epithelial cells were increased in IIP compared with normal lung parenchyma by immunohistochemistry. The results of TUNEL and electron microscopy suggested that apoptotic cells were predominantly epithelial cells. TUNEL-positive cells in % of epithelial cells were significantly increased in IIP compared with normal lung parenchyma, and significantly correlated with cytochrome c release from the mitochondria and with the expression of cleaved caspase-3 in epithelial cells. We conclude that mitochondria-mediated apoptosis may be involved in the pathophysiology of IIP.
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PMID:Mitochondria-mediated apoptosis of lung epithelial cells in idiopathic interstitial pneumonias. 1248 Sep 19

Discrimination of well-differentiated pulmonary adenocarcinoma from reactive bronchioloalveolar epithelium can be difficult on routine histology, especially with small biopsies. Ancillary studies to help in this distinction are desirable. p63, a p53-homologous nuclear protein, is a marker of reserve cells of the bronchus and terminal lobular unit. In this study, 33 cases of adenocarcinoma (20 open lung and 13 transbronchial/percutaneous biopsies) and 43 cases of benign lungs with fibrosis and metaplasia (22 open lung and 21 transbronchial/percutaneous biopsies) were studied for nuclear p63 expression by immunohistochemistry (Dako, Carpinteria, CA, USA). Five additional cases each of atypical adenomatous hyperplasia and adenosquamous carcinoma and three cases of squamous carcinoma (all open lung biopsies) were also stained. The diagnostic categories of benign lung conditions were usual interstitial pneumonia, parenchymal scar, cryptogenic organizing pneumonia and diffuse alveolar damage. In neoplastic cases, p63 positivity was calculated as percentage of all tumor cells examined. In areas of normal lung, p63 decorated the reserve cells of large and small airways and occasional cells of the distal lobular unit. In fibrotic reactive processes, an interrupted but distinct pattern of nuclear staining was present in all cases, with staining of basal cells of the airways as well as bronchiolar- and squamous-metaplastic epithelium (43/43, 100%). p63 immunoreactivity was less uniform in areas of acute lung injury within these cases. One adenocarcinoma and two cases of atypical adenomatous hyperplasia showed strong immunoreactivity (>80%), while three adenocarcinomas highlighted only rare tumor nuclei (<5% of tumor cells). Morphologic areas where p63 immunostaining was not helpful included the junction of normal lung and lepidic growth of adenocarcinoma, and retrograde spread of adenocarcinoma into small airways. Our results highlight the differential expression of p63 across various bronchioloalveolar lesions. Moreover, p63 may be helpful in distinguishing reactive from neoplastic glandular proliferations in the lung.
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PMID:p63 expression in assessment of bronchioloalveolar proliferations of the lung. 1520 81


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