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)

The p53 homologous squamous stem-cell regulatory protein p63 is expressed in squamous carcinomas but is not characteristically detected in small-cell carcinomas (SCCs). A panel of thyroid transcription factor (TTF) 1 and p63 has been shown to be useful in distinguishing SCCs from poorly differentiated squamous carcinoma of the lung (PDSLC) in small biopsies and cytological cell blocks. Because tumor samples frequently are limited to cytological smears, we attempted to detect p63 in destained slides from a spectrum of pulmonary malignancies. Archival alcohol-fixed smears from 60 cases of cytologically diagnosed malignancies in bronchoscopically (n = 59) or fine-needle aspiration-obtained specimens (n = 1) were destained in acid alcohol, postfixed in 10% formalin, subjected to citrate-based antigen retrieval, and immunostained by exposure to anti-p63 monoclonal antibody 4A4, followed by reagents from a streptavidin-biotin immunoperoxidase kit, and diaminobenzidine as the chromogen. Postfixation in 10% formalin was found to be necessary for immunostaining. Normal ciliated and goblet cells were p63 negative, but reserve cells were p63 positive. All cases of squamous-cell carcinoma were positive for p63. Of 10 tumor samples originally diagnosed as SCC, only 6 samples were p63 negative and 4 samples exhibited positive staining. However, proper interpretation of the immunohistochemical (IHC) staining pattern and careful scrutiny of the cytological features and biopsy specimens in three of four cases led us to reclassify three cases into PDSLC. All adenocarcinomas (ACAs; n = 12), large-cell carcinomas (n = 4), and metastatic ACAs (n = 5) were p63 negative. Positive staining was seen in 9/16 tumors designated as non-SCCs; these tumors were not classified further into distinct histological categories.p63 staining in destained slides may be of value in facilitating the differential diagnosis between PDSLC and SCC. Criteria for conservative interpretation of results are discussed and include examination of reserve cells and ciliated cells on the same slide as internal positive and negative controls.
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PMID:p63 immunostaining in destained bronchoscopic cytological specimens. 1575 65

n-3 polyunsaturated fatty acids (PUFAs) have been shown to exert beneficial effects in the prevention of cardiovascular disease, inflammation, and on tumor growth. To investigate effects of PUFAs on proliferation and apoptosis in endothelial cells, we tested the n-3 PUFA docosahexaenoic acid (DHA) and the n-6 PUFA arachidonic acid (AA) in human umbilical vein endothelial cells (HUVEC). The mitochondrial membrane potential (MMP) and the production of reactive oxygen species were examined by flow cytometry. Phosphorylation of p53 or p38 MAP kinase, and total levels of p53 were measured by Western blot. DNA binding activity of p53 was analyzed with a TransAM transcription factor assay kit. Tube formation was assessed on Matrigel. In proliferating HUVEC, but not in confluent cells, DHA reduced cell viability and induced apoptosis, as demonstrated by increases in membrane leakage (propidium iodide (PI) staining), Annexin-V binding, sub G(1) phase in the cell cycle, and TUNEL-positive cells. AA had no effect on these parameters. In addition to a reduced MMP and increased reactive oxygen species, phosphorylation of p38 and p53 (serine 15) and impaired DNA binding of p53 were observed. There was no change in total levels of p53. The p38 inhibitor SB203580 had no effect on Annexin V binding. DHA also attenuated HUVEC tube formation. Taken together, DHA induces apoptosis in proliferating, but not in resting HUVEC, potentially via the phosphorylation of p53, resulting in decreased p53 DNA binding. The results suggest that anti-angiogenic effects of DHA may be due to induction of apoptosis in proliferating endothelial cells.
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PMID:Docosahexaenoic acid induces apoptosis in proliferating human endothelial cells. 1579 39

The transmembrane-tyrosine-kinase receptor, c-kit, is involved in cell differentiation and has been found to be expressed in normal human cell types and solid tumors. This study was designed to investigate the effects of c-kit expression on: 1) tumor proliferation and apoptosis, and 2) survival in patients with high-grade advanced stage ovarian serous carcinoma (OSC). We identified 118 patients with high-grade advanced stage OSC from our files. Clinical data, including demographics and overall survival, were collected. Immunohistochemical panel consisting of c-kit, ki-67, p53, and bcl-2 was performed. C-kit was categorized as positive if any cytoplasmic or membranous staining pattern was identified. Correlation between c-kit expression and the other markers was performed. Survival analysis was performed using COX proportional hazards regression and Kaplan-Meier test. Of 118 cases, 25 (21.2%) expressed c-kit. Of 93 c-kit-negative tumors, 87.1% had a high proliferation index. High p53 and bcl-2 expression was identified in 96 (81.4%) and 59 (50%) cases respectively. No significant statistical correlation was identified between c-kit and apoptosis markers. Tumors lacking c-kit expression showed a trend toward having high proliferation index, but this did not achieve statistical significance (p = 0.07). Of the seven variables included in the multivariate survival analysis, only c-kit (odds ratio, 2.12; 95% confidence interval, 08-4.17; p = 0.02) and ki-67 (odds ratio, 1.9; 95% confidence interval, 1.1-3.1; p = 0.03) showed an independent statistically significant impact on survival. High-grade advanced stage OSC lacking c-kit expression correlates with poor outcome. Interestingly, cases lacking c-kit expression also showed a trend to have high proliferation index.
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PMID:The impact of c-kit and ki-67 expression on patients prognosis in advanced ovarian serous carcinoma. 1596 97

Smoking is a major cause of human lung cancer. Past studies suggest that apoptosis might influence the malignant phenotype, but little is known about the association between apoptosis and cigarette smoke (CS)-induced lung pathogenesis. Using an in situ cell death detection kit (TA300), the association of CS with apoptosis was determined in a concentration-dependent manner. Furthermore, the expression of related proteins were investigated in the terminal bronchiole areas of the lung tissue from rats exposed to CS. Results showed that the expression of phosphotyrosine proteins was increased significantly in lung tissue of rats exposed to CS from 5 to 15 cigarettes. Using Western blotting and immunoprecipitation assay, Fas, a death receptor, was proved just be one of these phosphotyrosine proteins. CS triggered activation of MAP kinase (p38/JNK or ERK2) pathway, which led to Jun or p53 phosphorylation and FasL induction links Fas phosphorylation. Further, smoke treatment produced an increase in the level of proapoptotic proteins (Bax, t-Bid, cytochrome c and caspase-3), but a decline in Bcl-2, procaspase-8 and procaspase-9 proteins. Thus, CS-induced apoptosis may result from two main mechanisms, one is the activation of p38/JNK-Jun-FasL signaling, and the other is stimulated by the stabilization of p53, increase in the ratio of Bax/Bcl-2, release of cytochrome c; thus, leading to activation of caspase cascade.
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PMID:Induction of apoptosis in the lung tissue from rats exposed to cigarette smoke involves p38/JNK MAPK pathway. 1597 Feb 77

Nitric oxide has been reported to have cytotoxic effects in several tumor cells. The objective of this study was to investigate the effects of exogenous nitric oxide on apopotosis in oral squamous cell carcinoma cells and to reveal its possible mechanism. Tca8113 cells were cultured with various concentrations of nitric oxide that were released from sodium nitroprusside (SNP). Nitrite/nitrate levels in the culture supernatant were determined using a commercial available nitric oxide kit. Cellular proliferation was determined by MTT assay. Apoptosis was detected by flow cytometry. Expression of inducible nitric oxide synthase (iNOS) was determined by immunocytochemistry. p53 expression was assessed by Western blot. SNP can release nitric oxide into the culture medium in a dose-dependent manner. Nitric oxide remarkably inhibits proliferation in a dose and time-dependent manners and lead to apoptosis of the Tca8113 cell. The p53 expression was elevated accompanying by the increased apoptotic cells. No difference of iNOS was found whether or not the cells were treated with SNP. Exogenous nitric oxide had an inhibitory effect on Tca8113 cells proliferation in a dose and time-dependent manners and possibly via p53 dependent apoptosis pathway. Exogenous nitric oxide had no significant effect on cellular iNOS protein.
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PMID:Nitric oxide induces oral squamous cell carcinoma cells apoptosis with p53 accumulation. 1597 83

The neural crest-derived mesectoderm gives rise to physiologic apoptosis areas in early vertebrate embryos. Certain teratologic agents increase this phenomenon. The purpose of this work was to detect caspase 3 (which is associated with the apoptosis cascade) and p53 in cell death areas, both during physiological apoptosis and during apoptosis induced by three agents (retinoic acid, methyl-triazene, irradiation). Antibody revelation was performed using the aBC peroxidase kit. Quantifications were also performed on histological sections. We observed caspase 3 uptake on some apoptotic and preapoptotic cells in control embryos, and in the embryos exposed to the three teratogens. Immunoreactivity generally preceded the development of cytological features of apoptosis. However, p53 was expressed only in the embryos exposed to ionizing radiation and methyl-triazene (an alkylating agent), but not significantly in embryos exposed to retinoic acid. The present results throw some light on apoptosis mechanisms in several teratologic conditions.
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PMID:[Expression of caspase 3 and p53 during physiological apoptosis and apoptosis induced by three teratologic agents during early craniofacial development of the mouse embryo]. 1611 Jul 44

Lung disease is the leading and second-leading cause of death in women and men in Taiwan, respectively. Epidemiological studies conducted in Taiwan have shown that cigarette smoking is the principal risk factor of lung disease, but little is known about the association between apoptosis and cigarette smoke (CS)-induced lung pathogenesis. We designed an animal exposure system to study signal proteins involved in the process of apoptosis induced by smoking in rat terminal bronchiole. Rats were exposed to CS in doses of 5, 10, and 15 cigarettes, respectively, and the exposure lasted for 30 min, twice a day, 6 days a week for 1 month. Following which the rats were sacrificed and the lung tissues were analyzed by histopathological methods. The terminal bronchioles revealed mild to severe inflammation according to the doses of CS and marked lipid peroxidation, lymphocyte infiltration, congestion, and epithelial emphysema of alveolar spaces were also noted. Using an in situ cell death detection kit (TA300), the association of CS with apoptosis was determined in a concentration-dependent manner. Immunohistochemical evaluation showed that CS treatment produced an increase in the cellular levels of Bax, t-Bid, cleaved caspase-3, phospho-p53, phospho-JNK, and FasL but a decline in Bcl-2 and Mcl-1 (p<0.001 for all) in rat terminal bronchioles. The results provided evidences suggesting that exposure to CS not only induced apoptosis, but also involved p53/Bax and JNK/FasL cascade pathway.
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PMID:Immunohistochemical detection of apoptotic proteins, p53/Bax and JNK/FasL cascade, in the lung of rats exposed to cigarette smoke. 1634 95

Diversity of P53 impact on tumor angiogenesis is due to the fact that wild-type P53 decreases expression of vascular endothelial growth factor (VEGF), but mutant P53 upregulates it. Therefore, we aimed at uncovering relations between preoperative serum levels of VEGF and P53 in colorectal cancer (CRC) patients. Preoperative blood samples of 125 CRC patients and 16 control healthy volunteers were examined with an ELISA-kit for serum P53 levels and VEGF. P53 did not correlate with VEGF in the whole group of CRC patients. However, P53 associated with VEGF in case of colorectal cancer patients, whose serum values of VEGF were higher than in controls (VEGF{H} >5.9333 pg/ml) (r=0.274, p<0.009). We revealed a positive correlation between P53 and VEGF{H} in subsets of poorly differentiated (G3) cancers (p<0.02), lymph node positive (p<0.007), pT3 or pT4 patients (p<0.004) without analogous relation in moderately differentiated (G2) tumors, node negative patients or pT1 or pT2 patients. P53 and IGF-I negatively correlated in all CRC patients (p<0.04) and VEGF{H} individuals of pT3 or pT4 (p<0.05) without any significant linkage in tumors of pT1 or pT2. The positive correlation between serum P53 and VEGF points at mutation of P53 and is a highly probable sign of poor prognosis in colorectal cancer. For now it can not be excluded that the binary analysis of serum P53 and VEGF could help select CRC patients endangered by rapid growth and lymph node metastases.
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PMID:P53 correlates positively with VEGF in preoperative sera of colorectal cancer patients. 1641 12

Embryonal sarcoma of the liver is a rare, aggressive malignant tumor that typically occurs in children and teenagers. Microscopic features include spindle, oval, or stellate cells with poorly defined cell borders, nuclear pleomorphism and multinucleation, and variable immunoreactivity to cytokeratin, vimentin, and alpha-1-antitrypsin. Intracellular and extracellular PAS-positive, diastase-resistant hyaline globules are commonly present. The authors evaluated a panel of IHC stains to better define the pattern of immunoreactivity in this tumor. Embryonal sarcomas of the liver were identified from archival files and were immunostained with antibodies: cytokeratin AE1/3, hepatocyte, SMMS, myogenin, calponin, h-caldesmon, desmin, S100, vimentin, CD34, C-kit (CD117), CD10, ALK-1, PE10, Bcl2, p53, and Ki-67. Six cases were identified. Patient age ranged from 6 to 24 years. Tumors ranged from 10 to 20 cm and contained spindled and epithelioid areas with PAS-positive, diastase-resistant globules and atypical cells with focal multinucleation. All cases showed immunoreactivity with vimentin and five showed immunoreactivity with Bcl2. Focal immunoreactivity was seen with cytokeratin AE1/3 in three cases, CD10 in four, calponin in two, desmin in one, and p53 in four. All tumors were negative with hepatocyte, myogenin, CD34, SMMS, h-caldesmon, PE10, ALK-1, and S100. No cytoplasmic staining was seen with C-kit. The proliferation index ranged from 30% to 95%. The diagnosis of embryonal sarcoma is based on typical morphologic features in a large liver tumor occurring in a young patient. The most useful IHC stains help to exclude tumors such as hepatoblastoma, hepatocellular carcinoma, embryonal rhabdomyosarcoma, and other sarcomas.
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PMID:Immunohistochemical analysis of embryonal sarcoma of the liver. 1678 89

HCV-associated hepatocellular carcinoma (HCC) is a common neoplasm in Egypt where genotype-4 is prevalent. In the present study the incidence and pattern of p53 mutations was assessed in relation to HCV-genotype- 4 in Egyptian HCC patients. We investigated 25 HCV positive HCCs for p53 mutations/overexpression in relation to HCV-NS3 by immunohistochemistry, SSCP and sequencing. Genotyping was done using LiPA-II and TRUGENE 5' NC' sequencing kit. Results were correlated to standard clinicopathologic prognostic factors for HCC. Thirteen cases showed p53 overexpression, and 10 showed p53 mutation (13 mutations) by sequencing (72% concordance). The highest mutation rate was in exons 6 and 7 (30%) followed by exons 5 and 8 (20%). Mutations included 3 transitions, 5 transversions, 3 deletions, and 2 insertions. All exon 7 mutations were at codon 249 specific for AFB1 (AGG-->AGT, Arg-->Ser) and codon 248 specific for vinyl chloride contamination (CGG-->TGG, Arg-->Trp). Other mutations reported are novel. Immunostaining for HCV NS3 was detected in 19 cases independent of p53 mutation. p53 aberrations were significantly associated with poor prognostic factors for HCC. However, no specific pattern for p53 mutations was observed in HCV genotype 4-associated HCC and no significant relation between p53 mutations, HCV-NS3 expressions or any HCV sub-genotype-4 sequence.
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PMID:p53 mutation in HCV-genotype-4 associated hepatocellular carcinoma in Egyptian patients. 1723 48


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