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 results of immunohistochemical expression of p53 protein in 106 invasive breast cancers were correlated with conventional pathologic prognostic parameters. Archival formalin-fixed, paraffin-embedded tissue sections of these cases were stained with a monoclonal antibody (Ab-2), raised against p53 protein using a peroxidase-labelled streptavidin biotin kit. Fifty-six (53%) showed positive nuclear staining; 31 were considered weakly, 21 moderately and 4 strongly positive. Forty-three (77%) of these positive cases stained less than 50% of the tumor cells, with a significant association between intensity and proportion of nuclei stained (p<0. 05). p53 staining also correlated with histologic grade (p<0.005) but not with tumor size nor clinical stage (p>0.05). The follow-up data did not reveal any statistically significant survival advantage for patients with p53 negative tumors.
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PMID:Immunohistochemical expression of p53 protein in invasive breast carcinoma: clinicopathologic correlations. 1042 20

Inactivation of the p53 tumor suppressor protein has been observed in a large number of human cancers. Overexpression of p53 induces either growth arrest or programmed cell death (apoptosis). The growth arrest function of p53 is mediated by induction of p21 (WAF1/CIP1), but the mechanisms underlying p53-dependent apoptosis are still largely unknown. To investigate these mechanisms, we have identified six differentially expressed transcripts in a human colon cancer cell line undergoing p53-dependent apoptosis. One of the p53-responsive genes showed significant homology to Drosophila peroxidasin, an extracellular matrix-associated peroxidase, and is likely to be its human homologue. Our results suggest a possible connection between p53-dependent apoptosis and the production of reactive oxygen species.
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PMID:Isolation of differentially expressed cDNAs from p53-dependent apoptotic cells: activation of the human homologue of the Drosophila peroxidasin gene. 1044 17

Hairless SKH-1 mice were exposed once to UVB light (180 mJ/cm2), and mechanistically important early adaptive responses in the epidermis were evaluated by immunohistochemical and morphological methods. Interrelationships in the time course for these UVB-induced responses were examined. The number of epidermal cells with DNA strand breaks (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive cells) or with thymine dimers increased to maximal levels within 30 min after UVB. The number of cells with DNA strand breaks located specifically in the basal layer of the epidermis was increased substantially by 3-30 min after UVB and gradually increased further over the next 5.5 hours. DNA strand breaks specifically in the basal layer of the epidermis were increased maximally at 6 h after UVB. The number of epidermal cells with DNA strand breaks or thymine dimers decreased markedly between 12 and 36 h. Pyrimidine (6-4) pyrimidone photodimers (6-4 photoproducts) in isolated epidermal DNA were increased immediately after irradiation of the mice with UVB and decreased markedly during the next 6 h. Exposure to UVB caused a rapid 8-fold increase in the number of epidermal cells with the DNA mismatch repair protein, MSH2 (within 30-60 min), and the level of MSH2-positive cells remained elevated for at least 48 h. These observations suggest a possible role of MSH2 in the repair of UVB-induced DNA damage. The number of epidermal cells with wild-type p53 protein started to increase at 1 h after UVB exposure and reached maximal levels by 8-12 h. The number of p53-positive cells fell markedly between 24 and 48 h. The time course for UVB-induced increases in the number of p53-positive cells was paralleled very closely by the time course for UVB-induced increases in the number of cells with p21(WAF1/CIP1), increases in morphologically distinct apoptotic sunburn cells, and decreases in the number of epidermal cells with bromodeoxyuridine (BrdUrd) incorporation into DNA. Although the start of UVB-induced increases in the number of p21(WAF1/CIP1)-positive cells was similar to that for the increase in p53-positive cells and very high levels of p21(WAF1/CIP1)-positive cells were observed at 8-12 h, maximal increases in p21(WAF1/CIP1)-positive cells were not achieved until 24 h after UVB irradiation (approximately 12 h after the peak value for p53). Myeloperoxidase-positive epidermal cells started to increase by 30 min after UVB exposure, and maximal numbers of myeloperoxidase-positive epidermal cells were observed at 2 h after UVB (18-fold higher than in nonirradiated control mice). An increased level of epidermal peroxidase enzyme activity in the epidermis was also observed from 1 to 24 h after exposure of the mice to UVB. Although neutrophil infiltration into the epidermis was not seen after exposure to UVB, neutrophil infiltration into the dermis (inflammatory response) was observed from 4 to 144 h after UVB exposure. In contrast to the marked inhibitory effect of UVB on BrdUrd incorporation into the DNA of epidermal cells observed at 8-12 h after UVB irradiation (>90% inhibition), BrdUrd incorporation into the DNA of epidermal cells was markedly increased (approximately 30-fold increase in the number of BrdUrd-positive cells) at 48 h after UVB exposure, and increases in epidermal cell layers and epidermal thickness (hyperplasia) were also observed. These later effects were associated with regeneration of the damaged epidermis.
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PMID:Time course for early adaptive responses to ultraviolet B light in the epidermis of SKH-1 mice. 1049 13

The present study examined the immunohistochemical expression of human AP endonuclease 1 (HAP1/Ref-1), the major endonuclease in the repair of apurinic/apyrimidinic (AP) sites in cellular DNA, in normal lung and lung carcinomas. Cellular expression of HAP1 was determined using a standard avidin-biotin-peroxidase complex (ABC) technique and an anti-HAP1 rabbit polyclonal antibody on paraffin-embedded tissue sections from normal lung and in 103 primary non-small cell lung carcinomas (NSCLCs). In normal lung, the staining for HAP1 was found to be both nuclear and cytoplasmic in the pneumocytes of the alveoli. Superficial ciliated cells of the bronchial epithelium presented cytoplasmic staining, while staining for the basal cells was mostly nuclear. Bronchial glandular cells demonstrated mixed nuclear and cytoplasmic staining. Lung carcinomas showed all patterns of expression for HAP1. Loss of HAP1 expression was associated with low proliferation index (p=0.01) and with squamous histology (p=0.04). In squamous carcinomas, a significant correlation was observed between positive nuclear HAP1 and negative p53 expression (p=0.03). A survival benefit was seen in patients presenting nuclear HAP1 expression and those presenting the nuclear HAP1+/p53- phenotype (p=0.01 and 0.007, respectively). It is concluded that nuclear HAP1 localization may be relevant to its role as a DNA repair protein and/or to the recently proposed role as an activator of wild-type p53, and thus to the better outcome seen in this group of patients.
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PMID:Nuclear localization of human AP endonuclease 1 (HAP1/Ref-1) associates with prognosis in early operable non-small cell lung cancer (NSCLC). 1054 96

The aim of the study was to determine whether the expression of the cell cycle markers p53, MDM2, p21, and Ki-67 was predictive of superficial bladder cancer recurrence and to compare the relative predictive power for tumor recurrence of a cell cycle index based on the number of abnormally expressed cell cycle markers with a clinicopathological index based on primary clinical tumor characteristics. The expression of p53, MDM2, and p21 proteins and the value of the Ki-67 index were analyzed for 244 patients. One hundred ninety-four lesions were determined to be superficial papillary tumors (pTa), whereas 50 tumors invaded the lamina propria (pT1). Tumor grade was noted low (grade 1) in 83 cases and high (grades 2-3) in 161 cases. An avidin-biotin peroxidase method was performed using monoclonal antibodies against p53, MDM2, p21, and Ki-67 antigens after antigen retrieval treatment of formalin-fixed specimens. The cell cycle marker index was created using the number of abnormally expressed cell cycle markers according to the following cutoff points: p53 (>5%), MDM2 (>20%), p21 (<5%), and Ki-67 (>10%). The clinicopathological index was created using the following adverse tumor characteristics: grades G2-G3, stage pT1, multifocality, and diameter of tumors > 3 cm. Cox regression models were used to calculate the relative risks and their 95% confidence intervals associated with disease recurrence for the clinicopathological index and the cell cycle marker index. The chi2 test was performed to describe the correlation between the Ki-67 index and p53, MDM2, and p21 protein expression. Kaplan-Meier survival curves were generated to demonstrate the disease-free survival according to these two prognostic indexes. The clinicopathological index was a strong, independent predictor of disease recurrence where tumors with three or four adverse tumor characteristics at initial resection had over four times the risk of recurrence than tumors with no risk factors (P for trend = 0.0001). A strong correlation was observed between the Ki-67 index >10% and both MDM2 and p21 proteins. MDM2 was overexpressed in 106 tumors (43%), and p53 was overexpressed in 47 (19%); Ki-67 was >10% in 171 cases (70%). Thirty-nine tumors (16%) were p21 negative. The risk of recurrence increased slightly with the number of abnormally expressed cell cycle markers, but when the clinicopathological index was taken into account in multivariate analysis, the cell cycle marker index was not predictive of disease recurrence (P for trend = 0.72). The cell cycle markers studied provided no added prognostic information on disease recurrence after initial resection of papillary superficial tumors when the clinicopathological parameters were taken into account.
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PMID:Predictive value of cell cycle markers p53, MDM2, p21, and Ki-67 in superficial bladder tumor recurrence. 1600 76

Thyroid toxicity of iodide excess has been demonstrated in animals fed with an iodide-rich diet; in vitro iodide is cytotoxic, inhibits cell growth, and induces morphological changes in thyroid cells of some species. In this study, we investigated the effect of iodide excess in an immortalized thyroid cell line (TAD-2) in primary cultures of human thyroid cells and in cells of nonthyroid origin. Iodide displayed a dose-dependent cytotoxicity in both TAD-2 and primary thyroid cells, although at different concentrations, whereas it had no effect on cells of nonthyroid origin. Thyroid cells treated with iodide excess underwent apoptosis, as evidenced by morphological changes, plasma membrane phosphatidylserine exposure, and DNA fragmentation. Apoptosis was unaffected by protein synthesis inhibition, whereas inhibition of peroxidase enzymatic activity by propylthiouracil completely blocked iodide cytotoxicity. During KI treatment, reactive oxygen species were produced, and lipid peroxide levels increased markedly. Inhibition of endogenous p53 activity did not affect the sensitivity of TAD-2 cells to iodide, and Western blot analysis demonstrated that p53, Bcl-2, Bcl-XL, and Bax protein expression did not change when cells were treated with iodide. These data indicate that excess molecular iodide, generated by oxidation of ionic iodine by endogenous peroxidases, induces apoptosis in thyroid cells through a mechanism involving generation of free radicals. This type of apoptosis is p53 independent, does not require protein synthesis, and is not induced by modulation of Bcl-2, Bcl-XL, or Bax protein expression.
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PMID:Iodide excess induces apoptosis in thyroid cells through a p53-independent mechanism involving oxidative stress. 1065 Sep 40

This study detects and defines the patterns of p53 gene mutations in breast cancers. We analyse p53 gene mutations through comparing the results of single-strand-conformation-polymorphism (SSCP) and immunohistochemistry (IHC), and we try to define the differences between the results of SSCP and IHC. Twenty-seven fresh primary breast cancer tissues and eight normal breast tissues were studied. The IHC was done with the usual streptavidin-biotin peroxidase complement method by using monoclonal antibody DO-7. The results of staining was scored. The SSCP method was done by using Cold SSCP Electrophoresis System. Overexpressions of p53 protein were seven (25.9%) among 27 cancer cases on IHC. Four (57.1%) of seven cases were positive in SSCP. In SSCP, the mutations were detected in 10 (37%) among 27 cancer cases. The mutations were two in exon 5, one in exon 8, and seven cases in exon 7. All of 10 mutations were proved by sequencing analysis. Of them, only four (40%) were positive in IHC. We consider the IHC as a screening method for p53 gene mutations.
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PMID:Detecting p53 gene mutation of breast cancer and defining differences between silver staining PCR-SSCP and immunohistochemical staining. 1071 13

The aim of the present study was the evaluation of the immunohistochemical expression of the apoptosis-inhibiting protein bcl-2, the cell-cycle-related antigen Ki-67 and the p53 protein, which is involved both in cell cycle and apoptosis regulation, in the lining epithelium of glandular odontogenic cysts of the jaws. Formalin-fixed and paraffin-embedded tissue sections of three glandular odontogenic cysts and six dentigerous cysts were immunostained with a standard avidin-biotin peroxidase procedure, after microwave antigen retrieval. The glandular odontogenic cysts showed immunoreactivity for bcl-2 protein in the basal and suprabasal layers, while staining in dentigerous cysts was basal or focal. Most mucous cells and superficial cuboidal cells were negative. The percentage of Ki-67- or p53-positive cells was lower in glandular odontogenic cysts compared with dentigerous cysts. The findings suggest that the biological behavior of glandular odontogenic cysts may be associated with deregulation of cell death in the lining epithelium, while cell proliferation and p53 status do not seem to play a significant role.
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PMID:Immunohistochemical study of bcl-2 protein, Ki-67 antigen and p53 protein in epithelium of glandular odontogenic cysts and dentigerous cysts. 1073 41

We have analyzed the tumor biopsies of 45 patients with bladder cancer for p53 mutations by direct sequencing. In addition to N-acetyltransferase-2 (NAT2) and GSTM1 allelisms, which were examined previously, we have analyzed the genetic polymorphisms of GSTT1, GSTP1, COMT, NQO1, TS-SULT and MPO in buffy coat DNA using PCR-based methods. All subjects were interviewed through a questionnaire on smoking, dietary habits and other risk factors. No specific pattern was evident for p53 mutations. Eight out of ten mutations occurred in grade 3 tumors. All p53 mutations occurred in subjects with the COMT mutated allele (p=0.03). The prevalence of cases with p53 mutations was 3.5-fold higher in subjects with wild type than in those with variant GSTP1 alleles (p=0.03). The other polymorphisms investigated were not associated with p53 mutations.
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PMID:Impact of polymorphisms in xeno(endo)biotic metabolism on pattern and frequency of p53 mutations in bladder cancer. 1076 40

Ki-67 and P53 expression were studied using immunohistochemistry on tissue samples obtained during transurethral electroresection or needle biopsy in 62 patients with prostatic lesions: group 1 (n = 15)--benign prostatic hyperplasia (BPH), group 2 (n = 10)--high-grade prostatic intraepithelial neoplasia (PIN 3), group 3 (n = 10)--low-grade prostatic carcinoma (PC, Gleason score 2-4), group 4 (n = 12) intermediate-grade prostatic carcinoma (PC, Gleason score 5-7) and group 5 (n = 15) high-grade prostatic carcinoma (PC, Gleason score 8-10). Moreover, in the groups examined the associations between expression of Ki-67 and P53 were analysed. Paraffin-embedded tissue samples were immunostained with monoclonal antibody anti-P53 and polyclonal antibody anti-Ki-67 using avidinbiotin-peroxidase method. Our study revealed lack of Ki-67 and P53 immunoreactivity in BPH. Only 3 out of 10 high-grade PIN exhibited Ki-67 positivity, but there was no immunopositivity of P53 protein in this group. Although immunopositivity of Ki-67 increased with the histological grade of prostatic cancer, the differences in Ki-67 expression between intermediate and high-grade cancer did not reach statistical significance. A similar level of Ki-67 reactivity in intermediately-differentiated and poorly-differentiated prostate cancer suggests a similar biology of these cancers. P53 protein positivity was noted in 62.2% cases of prostate cancer. Moreover, the highest level of P53 accumulation in intermediate-grade carcinomas may predict the aggressive progression and risk of metastases in these cases. No significant differences in P53 immunopositivity between low-grade and high-grade PC were noted. Interestingly, only in low-grade PC there was a significant positive correlation between expression of Ki-67 and P53 protein.
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PMID:Ki-67 antigen and P53 protein expression in benign and malignant prostatic lesions. Immunohistochemical quantitative study. 1083 1


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