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)

Intense research using animal models has indicated that chemically-induced rat liver cancer proceeds through multiple, distinct stages that can be characterised morphologically and biochemically. Primary human liver cancer, with hepatitis B and other environmental factors such as poor nutrition and food contaminating mycotoxins as contributing etiological factors, is one of the major causes of cancer deaths in African, Asian and some Western countries. Recent advances in surgical and diagnostic techniques have also allowed the identification of potential morphological precursors of primary human liver cancer, and suggested a model consistent with the concepts of initiation--promotion--progression as in the rat. The expression of proliferating cell nuclear antigen (PCNA), silver-staining nucleolar organiser regions (AgNOR), oncogenes and the tumor suppressor gene p53 in preneoplastic and neoplastic lesions of rat and human livers is presently reviewed. This undertaking is an attempt to evaluate whether the current knowledge regarding molecular mechanisms of carcinogenesis is sufficient to permit the use of these molecular parameters as 'intermediate' markers in studies of risk assessment and cancer prevention, without having to resort to tumor appearance as an end-point.
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PMID:The potential for the use of cell proliferation and oncogene expression as intermediate markers during liver carcinogenesis. 760 May 46

The clinical and immunohistochemical features of supratentorial (5 patients) and cerebellar (1 patient) glioblastomas, in which giant cells were conspicuous were examined. Three of the patients died within 26 months after the first treatment, and the follow-up period is presently 1 year or less in the remaining patients. The giant cells either showed large and bizarre nuclei or were multinucleated. Both giant and smaller cells excluding neuronal, endothelial and infiltrative cells were positive for GFAP, vimentin, and alpha-1 anti-chymotrypsin. The strong positivity for PCNA staining indicated that the capacity of the giant cells to synthesis DNA was preserved. DNA fragmentation, measured by the terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine-5'-triphosphate (dUTP)-biotin nick end labeling method, was observed in only 1 patient, who had received radiotherapy just before biopsy, and none of the patients showed bcl-2 positivity. Mutant type of p53 tumor suppressor gene was observed in the giant cells of 3 patients. Giant cell in glioblastoma is of glial origin, synthesizes DNA, and its progression may be related to tumor suppressor gene.
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PMID:Immunohistochemical study of giant cell in glioblastoma. 760 97

Nuclear DNA ploidy analysis, p53 immunohistochemical overexpression and PCNA Labeling Index (PCNA LI) were studied in 80 cases of resected "single nodular" human hepatocellular carcinoma (HCC) tissue sections. Aneuploid pattern was found in forty-six cases (57.7%) and p53 overexpression in fifteen cases (18.8%). The rate of aneuploid pattern was significantly higher in patients with carcinomas more than 2 cm in diameter, fc-inf positive growth and more than Stage II. p53 overexpression was not found in patients with well-differentiated HCCs and Stage I. Positive rate of p53 overexpression was significantly higher in patients with HCV-Ab positive and PCNA LI > or = 40%. It was high in patients with vp-positive, vv-positive and aneuploid pattern. PCNA LI of HCCs were significantly higher in patients with HBs-Ag positive, high serum AFP level, massive type and single nodular type with proliferation into surrounding area, fc-inf positive, im-positive, Stage III + IV, aneuploid pattern and p53 overexpression. The postoperative prognoses of patients with aneuploid pattern and PCNA LI > or = 40% were significantly poorer than those of the diploid one and PCNA LI < 40% in cumulative survival rates. Those prognoses were remarkably poorer in the early postoperative period. Patients with p53 overexpression had poorer prognosis than those with no p53 overexpression in the early postoperative period. These results suggest that nuclear DNA ploidy analysis, p53 immunohistochemical overexpression and PCNA LI were useful markers of biological malignant potentials in "single nodular" human HCCs.
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PMID:[DNA ploidy pattern, p53 immunohistochemical overexpression and PCNA labeling index in "single nodular" human hepatocellular carcinomas from the viewpoint of biological malignant potential]. 761 70

Gastric dysplasia (high-grade, HGD, and low-grade, LGD) and normal mucosa were tested for anti-p53, anti-Ki-67 and anti-PCNA monoclonal antibodies on paraffin sections, and for relative AgNOR area and number on semithin Epon-Araldite sections. The proliferative compartment in normal mucosa was restricted to the middle layer corresponding to the neck-isthmus region. In LGD and HGD there was an expansion of this compartment to the lower and upper layers of mucosa, and in HGD in particular to the upper layer. p53 was always negative in LGD as well as in normal mucosa, while it was positive in 34 out of 51 cases of HGD. The most discriminant variables between LGD and HGD were relative AgNOR area and the percentages of MIB-1, p53 and PCNA. In p53-positive HGD the highest percentages of PCNA and MIB-1 were in the middle and upper layers (PCNA) or the upper layer (MIB-1), while in p53-negative HGD cases cell proliferation was maximal in the middle layer, although also present in the upper layer. The majority of cases of LGD did not demonstrate cell proliferation in the upper layer, but 5 cases behaved similarly to the p53-negative HGD cases. No significant correlations were found among percentages of MIB-1 and of PCNA and relative AgNOR area and number.
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PMID:Cell proliferation patterns and p53 expression in gastric dysplasia. 762 88

We report 25 cases of a peculiar sclerosing epithelioid variant of fibrosarcoma (SEF) simulating an infiltrating carcinoma. The tumors occurred primarily in the deep musculature and were frequently associated with the adjacent fascia or periosteum. The patients' ages were 14 to 87 years (median, 45). Fourteen were male and 11 female. The tumors were located in the lower extremities and limb girdles (12 cases), trunk (9), upper limb girdles (2), and neck (2). They measured 2 to 14.5 cm in greatest dimension (median size, 7 cm) and were gray to white and firm. Histologically, the lesions were characterized by a proliferation of rather uniform, small, slightly angulated, round to ovoid epithelioid cells with sparse, often clear cytoplasm arranged in distinct nests and cords. In all cases there was prominent hyaline sclerosis, sometimes reminiscent of osteoid or cartilage and foci of conventional fibrosarcoma. Occasional myxoid zones with cyst formation and foci of hyaline cartilage, calcification, and metaplastic bone were also seen. Mitotic figures were generally scarce. Vimentin was detected in 13 of 14 cases, epithelial membrane antigen in seven, S100 protein in four, and neuron-specific enolase in two. Cytokeratins were detected with AE1/AE3 and CAM 5.2 in two cases. Leukocyte common antigen, CD68 antigen, HMB45, desmin, and alpha-smooth muscle actin were negative in all cases. In 13 of 14 cases, 75% or more of the cells stained for proliferating cell nuclear antigen (PCNA). Ki67 immunostaining with MIB 1 showed low proliferative activity in all cases, averaging 5% of tumor cells or less. In all cases, p53 was detected by immunohistochemical methods; bcl-2, an antiapoptosis marker, was detected in more than 90% of the cells in 11 of 12 cases. Ultrastructurally, both the epithelioid and spindled tumor cells had features of fibroblasts. Follow-up in 16 cases ranging from 13 months to 17 years 3 months (median, 11 years 4 months) revealed persistent disease or local recurrences in 53% of patients and metastases in 43%. The metastases were to the lungs (4 cases), skeleton (3), chest wall/pleura (3), pericardium (1), and brain (1). Four patients died of disease, four were alive with disease, two were known to be alive but disease status unknown, and six had no evidence of further disease at last follow-up. The data suggest that SEF is a relatively low-grade fibrosarcoma; yet it is fully malignant despite the presence of histologically benign-appearing foci. The proliferation markers PCNA and Ki67 did not correlate with prognosis.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Sclerosing epithelioid fibrosarcoma. A variant of fibrosarcoma simulating carcinoma. 766 Dec 86

Elective cervical lymphadenectomy often is performed for laryngeal carcinoma to eliminate metastatic disease that escapes clinical and radiographic detection. We investigated characteristics of the primary tumor that might predict cervical lymph node status. We obtained archival tissue from 88 laryngectomies--65 with concurrent cervical lymphadenectomies. Of the 40 clinically negative necks that were dissected, 17% showed lymph node metastasis by pathologic examination. The primary tumors were examined immunohistochemically for expression of epidermal growth factor receptor (EGFR), p53, cathepsin D, proliferating cell nuclear antigen (PCNA), and Ki-67-specific antigen, and by flow cytometry for DNA ploidy-cell cycle analysis. Seventy-seven percent of the cases showed aberrant p53 staining, 99% expressed EGFR, 40% produced cathepsin D, 29% were aneuploid, and 54% had a moderate or high synthesis phase fraction (SPF). High grade, aneuploidy, and tumor vascular invasion independently predicted cervical node metastasis (p < .04 each). Supraglottic locale (p < .16) and a raggedly infiltrating invading margin (p < .13) were weakly associated with node positivity. Advanced clinical T status, the expression of EGFR, p53, and cathepsin D, the PCNA and Ki-67 indices, and SPF did not correlate with node metastasis. The presence of cervical node metastasis predicted poor disease-free (p < .005) and overall survival (p < .04). Advanced clinical T status correlated with brief overall survival (p < .02). Tumor site, histopathologic parameters, ploidy, SPF, PCNA and Ki-67 indices, and the expression of p53, EGFR, and cathepsin D did not affect survival. The presence of vascular invasion, high grade, and aneuploidy may help identify which patients would benefit from elective cervical lymphadenectomy. The correlation of cervical lymph node status and clinical T category with survival confirms the results of previous studies.
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PMID:Cervical lymph node status and survival in laryngeal carcinoma: prognostic factors. 766 16

p21, a p53-induced gene product that blocks cell cycle progression at the G1 phase, interacts with both cyclin-dependent kinases and proliferating cell nuclear antigen (PCNA). PCNA functions as a processivity factor for DNA polymerases delta and epsilon and is required for both DNA replication and nucleotide excision repair. Previous studies have shown that p21 inhibits simian virus 40 (SV40) DNA replication in HeLa cell extracts by interacting with PCNA. In this report we show that p21 blocks nucleotide excision repair of DNA that has been damaged by either ultraviolet radiation or alkylating agents, and that this inhibition can be reversed following addition of PCNA. We have determined that p21 is more effective in blocking DNA resynthesis than in inhibiting the excision step. We further show that a peptide derived from the carboxyl terminus of p21, which specifically interacts with PCNA, inhibits polymerase delta-catalyzed elongation of DNA chains almost stoichiometrically relative to the concentration of PCNA. When added at higher levels, this peptide also blocks both SV40 DNA replication and nucleotide excision repair in HeLa cell extracts. These results indicate that p21 interferes with the function of PCNA in both in vitro DNA replication and nucleotide excision repair.
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PMID:Inhibition of nucleotide excision repair by the cyclin-dependent kinase inhibitor p21. 766 22

The p53 tumor-suppressor protein binds DNA and activates the expression of a 21-kDa protein that inhibits both the activity of cyclin-dependent kinases and the function of proliferating cell nuclear antigen. Since p21 expression has been reported to increase 10- to 20-fold as human diploid fibroblasts lose the ability to replicate, we examined the expression and activity of p53 during replicative aging. Similar levels of total p53 mRNA and protein were expressed in low-passage (young) and high-passage (old) cells but both DNA binding activity in vitro and transcriptional activity of p53 in vivo were increased severalfold in high-passage cells. While the basis of increased p53 activity is presently unclear, it is not correlated with differential phosphorylation or changes in p53-mouse double minute 2 gene product interactions. These results provide evidence for the activation of a protein involved in the control of cell cycle checkpoints during cellular aging, in the absence of increased expression.
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PMID:Increased activity of p53 in senescing fibroblasts. 766 93

Bcl-2 expression has been evaluated immunocytochemically in a series of 33 medullary thyroid carcinomas (MTC) with long-term (mean, 10.3 years) follow-up. Twenty-six of 33 cases showed intense bcl-2 immunoreactivity in more than 25% neoplastic cells. Bcl-2 immunoreactivity did not correlate with several clinicopathologic parameters including sex and age of the patients, sporadic or familial disease, tumor size and stage, amount of amyloid stroma, and immunoreactivity for calcitonin, chromogranin A, proliferating cell nuclear antigen (PCNA), N-myc, and p53. Lack of bcl-2 immunoreactivity, however, correlated significantly (P = .0001) with a shorter survival. Indeed, the seven patients with tumors devoid of bcl-2 immunoreactivity all died of disease within 8 years from the diagnosis. In multivariate analysis, lack of bcl-2 immunoreactivity was an independent predictor of worse prognosis (P = .001 for disease-free survival and P = .0001 for overall survival). None of the other clinicopathologic variable investigated proved to be an independent prognostic parameter. It is concluded that down-regulation of bcl-2 expression in MTC may identify a subset of tumors with a more aggressive clinical course.
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PMID:Prognostic value of bcl-2 immunoreactivity in medullary thyroid carcinoma. 767 94

Immunohistochemical stainings for EGFR, c-erbB-2, p53 and PCNA were performed on 36 and 30 cases of intramucosal and advanced carcinomas of large intestine. Positive rate was 58.3%, 41.6%, 58.3% and 60.6% for EGFR, c-erbB-2, p53 and PCNA in the intramucosal cases, and 66.7%, 50%, 66.7% and 72.6% in the advanced ones, respectively. Relationship between EGFR and c-drbB-2 was more significant in the advanced carcinomas than that in the intramucosal ones. It seemed likely that relationship between p53 and c-erbB-2 was more significant than that between p53 and EGFR. Positive rate of PCNA was of intimate relationship among that of EGFR, c-erbB-2 and p53, and the positive rate increased in the advanced carcinomas.
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PMID:[Immunohistochemical study of PCNA, EGFR, c-erbB-2 and p53 in carcinomas of large intestine]. 767 43


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