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)

We analysed by immunohistochemistry the expression of p53 protein in a case of micro-invasive carcinoma of the conjunctiva. About 50% of tumor cells showed a strong nuclear positivity for p53. This suggests that p53 gene alterations play a role in the development of this type of tumor.
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PMID:p53 protein overexpression in a case of conjunctival micro-invasive carcinoma. 781 35

Since mutated p53 is one of the most frequent gene abnormalities in human cancer, we hypothesized that mutation of p53 may play an important role in growth and recurrence of pterygia, a dysplasia of the conjunctiva. Therefore, we compared pterygia of Japanese and Tunisian patients using antibodies against p53, p21 and proliferating cell nuclear antigen (PCNA). In Nagasaki, 21 pterygia of Japanese individuals were removed and in Gabes, 19 primary pterygia of Tunisian individuals. Positive staining of wild type p53 was not found in the Japanese pterygia, whereas 38.1% were positive for mutant p53, none were positive for p21 and 76.2% were positive for PCNA. The incidence of mutant p53-positive staining was 50.0% in males and 22.2% in females, which was statistically significant. In the 19 Tunisian patients, positive staining of wild type p53 was not found, whereas 36.8% were positive for mutant p53, 0% for p21 and 63.1% for PCNA. Differences between Japanese patients and Tunisian patients were not significant. There were 2 types of pterygium. One type did not show mutant p53 and the other showed mutant p53 caused by ultraviolet light. However, damage caused by p53-dependent programmed cell death of pterygium cells may lead to mutations in other genes which may allow the progressive multistep development of limbal tumors. It is possible that mutant p53-positive pterygia can develop into limbal tumors.
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PMID:Immunohistochemical study of p53, p21 and PCNA in pterygium. 1136 97

Squamous cell carcinoma of the conjunctiva is associated with sun exposure and often occurs in HIV-positive individuals. We have analysed TP53 mutations in 21 cases of squamous cell carcinoma and 22 controls with benign conjunctival lesions from a region (Uganda, Africa) with a high prevalence of heavy sun exposure and HIV infection. TP53 mutations were detected in 11 cases (52%) and 3 controls (14%). Seven of the mutations (6 in cases and 1 in controls) were CC-->TT transitions, a molecular signature of mutagenesis by solar UV rays. A similar prevalence (56%) of TP53 mutations was found in 18 squamous cell carcinoma cases positive for epidermodysplasia verruciformis human papillomavirus types. The prevalence of CC-->TT transitions reported here is the highest observed in any cancer type and matches that of skin cancers in subjects with xeroderma pigmentosum, an inherited disease with hypersensitivity to UV damage. These results confirm at the molecular level the causal role of solar UV rays in the aetiology of squamous cell carcinoma of the conjunctiva and suggest that infection with epidermodysplasia verruciformis types of human papillomavirus may act as a cofactor to increase the sensitivity of conjunctiva cells to UV-induced mutagenesis.
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PMID:TP53 mutations in squamous-cell carcinomas of the conjunctiva: evidence for UV-induced mutagenesis. 1538 13

Cell proliferation and programmed cell death are considered to be important events in carcinogenesis. The object of our study was to evaluate the expression of the Bcl-2 protein family (Bcl-2, Bak, Bax), p53, proliferating cell nuclear antigen (PCNA), and Ki-67 protein immunoexpression as well as the correlation between the examined markers and some clinicopathological features in papillomas and cancers of conjunctiva and eyelid. Forty-five squamous cell papillomas (SCP), 11 squamous cell cancers (SCC), and 27 basal cell cancers (BCC) were estimated. In the SCP group, p53 protein expression was observed in 30 cases (66.6%), Ki-67 in 14 (31.1%), PCNA in 44 (97.8%), Bcl-2 in 24 (53.3%), Bak in 28 (62.2%), Bax in 31 (68.9%), and Bcl-xl in 11 (100%). In the SCC group, p53 protein expression was evaluated in 8 cases (72.8%), Ki-67 in 2 (18.2%), PCNA in 8 (72.7%), Bcl-2 in 5 (45.4%), Bax and Bak both in 10 (90.9%), and Bcl-xl in 100%. In the BCC group, p53 protein expression was estimated in 23 cases (85.1%), Ki-67 in 13 (48.1%), PCNA in 26 (96.2%), Bcl-2 in 13 (48.1%), Bak in 21 (77.8%), Bax in 22 (81.5%), and Bcl-xl in 23 (85.2%). We observed a correlation between some clinicopathological features and the examined markers of apoptosis and cell proliferation, which seemed to be important events in cancer development.
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PMID:Expression of cell proliferation and apoptosis markers in papillomas and cancers of conjunctiva and eyelid. 1565 25

The human ocular surface is covered by the conjunctival, corneal and limbal stratified epithelia. While conjunctival stem cells are distributed in bulbar and forniceal conjunctiva, corneal stem cells are segregated in the basal layer of the limbus, which is the transitional zone between the cornea and the bulbar conjunctiva. Keratinocyte stem and transient amplifying (TA) cells when isolated in culture give rise to holoclones and paraclones, respectively. Keratinocyte replicative senescence ensues when all holoclones have generated paraclones which express high levels of p16(INK4a). In the present study, we show that enforced telomerase activity induces the bypass of replicative senescence in limbal and conjunctival keratinocytes, without the inactivation of the p16(INK4a)/Rb pathway or the abrogation of p53 expression. hTERT-transduced limbal and conjunctival keratinocytes are capable to respond to both growth inhibitory and differentiation stimuli, since they undergo growth arrest in response to phorbol esters, and activate p53 upon DNA damage. Following a sustained PKC stimulation, occasional clones of p16(INK4a)-negative cells emerge and resume ability to proliferate. Telomerase activity, however, is unable to induce the bypass of senescence in corneal TA keratinocytes cultured under the same conditions. These data support the notion that telomere-dependent replicative senescence is a general property of all human somatic cells, including keratinocytes, and suggest that telomerase activity is sufficient to extend the lifespan only of keratinocytes endowed with high proliferative potentials (which include stem cells), but not of TA keratinocytes.
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PMID:Telomerase activity is sufficient to bypass replicative senescence in human limbal and conjunctival but not corneal keratinocytes. 1567 13

Previously, we reported that pterygial epithelial cells show positive p53 staining by immunohistochemistry, and that they do not demonstrate apoptosis. We wished to determine whether the accumulation of p53 protein was caused by missense mutations in exons 5-8 of the TP53 gene, as is frequently the case in malignant tumours that contain high levels of abnormal p53. From 11 pterygia, epithelial cells were isolated by laser capture microdissection, or manually, in order to reduce the contribution of TP53 from normal cells. DNA from pterygial epithelial cells was amplified across exons 5-8 in 10 pterygia and across exons 5,7 and 8 in another pterygium. In 2 pterygia, all translated exons (2-11) were sequenced. No mutations were found, although normal polymorphisms in codon 72 were readily detected in 2 pterygia. RT-PCR was used to compare amounts of TP53 mRNA isolated from normal conjunctiva and pterygia from eight additional patients. We detected an approximate two-fold increase of TP53 RNA in pterygia compared to that in normal conjunctiva. Western blotting was used to compare amounts of p53 protein in pterygia and normal conjunctiva. Consistent with our previous immunohistochemical studies, amounts of p53 protein in pterygia, detected by the western blotting, were elevated compared to those detected in normal conjunctiva and corneal limbal epithelium. However, the TP53 gene in pterygia is not mutated, and therefore, the elevated levels of p53 protein must result from a different mechanism than that seen in malignant tumours containing TP53 missense mutations. The increased amount of p53 protein in pterygial cells does not cause apoptosis or block cell proliferation, suggesting that these normal p53 functions are inactivated in pterygia.
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PMID:Accumulation of p53 protein in pterygia is not accompanied by TP53 gene mutation. 1600 68

Squamous cell carcinoma (SCC), the most common primary malignant tumor of the conjunctiva, has a variable clinical presentation and immunohistochemical profile. Abundant cell cycles exist, including MIB-1 (Ki67 antigen), p16, p53, and p63, within the conjunctiva SCC. This investigation first reports the expressions of cell cycle markers in SCC. A retrospective study was conducted between December 1976 and June 2004, comprising 13 consecutive patients with conjunctiva SCC who were treated with surgical excision. Detailed clinical parameters were also reviewed. Overexpression of MIB-1, p16, p53, and p63 genes were studied by immunohistochemistry. Genechip containing 39 subtypes was used to elucidate human papillomavirus (HPV). The study group contained 13 (100%) men, with a mean age of 68+/-18 years and follow-up period of 20+/-17 months. The sample included four (33%) SCC located in the left eye and two (17%) recurrent SCC. Overexpression of the p53 and p63 was considerably higher than that of the p16 (P<0.01). HPV DNA was not detected in any of the 13 cases. This work first examined the immunohistochemical overexpression of cell cycle (MIB-1, p16, p53, and p63) in SCC. This investigation then showed that the expression of cell cycles in SCC was associated with key tumor clinicopathological features. This approach can help distinguish the potential roles of cell cycle in the development of SCC.
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PMID:Expression of cell cycle-regulatory proteins, MIB-1, p16, p53, and p63, in squamous cell carcinoma of conjunctiva: not associated with human papillomavirus infection. 1632 55

The t(14;18)(q32;q21) involving the MALT1/MLT and IGH genes has been identified recently as a recurrent abnormality in mucosa-associated lymphoid tissue (MALT) lymphomas. The frequency of secondary chromosomal aberrations in MALT lymphomas harboring the t(14;18) is largely unknown. We therefore analyzed six t(14;18)-positive MALT lymphomas (five parotid, one conjunctiva) by interphase fluorescence in situ hybridization for aneuploidies of chromosomes 3, 7, 12, 18, and X, gains or disruption of the CMYC/8q24 and BCL6/3q27 genes, as well as deletions of the retinoblastoma and TP53 tumor suppressor genes. Except for one MALT lymphoma of the parotid with trisomy 3, neither aneuploidies nor deletions were detected in any of our cases.
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PMID:Frequency of chromosomal aneuploidies and deletions of the RB and TP53 genes in MALT lymphomas harboring the t(14;18)(q32;q21). 1636 68

The expression pattern of VEGF, p53 and ICAM-1 was studied in conjunctiva of diabetic patients with and without retinopathy. All patients underwent a complete ophthalmic examination, including retinal fluorescein angiography. Indirect immunoperoxidase method was performed on 20 eyes of 20 patients with type II diabetes without DR and on 5 eyes of 5 patients with PDR. A control study was performed on 6 normal conjunctiva undertaken during cataract surgery. Immunoreactivity of VEGF, p53 and ICAM-1 was found in epithelial, fibroblast and vascular endothelial cells. For the same duration of diabetes, a strong to moderate or weak immunoreactivity was observed in the conjunctiva of patients without retinopathy. In patients with PDR, the expression was strong for all these proteins. The immunoreactivity was correlated between VEGF, p53 and ICAM-1. In the normal conjunctiva, a weak to negative immunostaining was observed. The presence of these proteins in the conjunctiva of diabetic patients without retinopathy may add new data in the pathogenesis of diabetic retinopathy. Further studies are needed to confirm this hypothesis.
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PMID:Immunohistochemical study of vascular endothelial growth factor (VEGF), tumor suppressor protein (p53) and intercellular adhesion molecule (ICAM-1) in the conjunctiva of diabetic patients. 1648 25

To determine whether the fibrovascular proliferation observed in pterygium, may be, at least in part, mediated by an increased activity of cholesterol metabolism. The correlation between lipid metabolism and rate of growth was studied in human normal conjunctival (NCF) and primary pterygium fibroblasts (PFs) in primary culture. The expression of two proliferation markers (Ki-67 and p53) was evaluated by immunohistochemical staining techniques. Proliferation was evaluated by [(3)H]thymidine incorporation and by immunohistochemical assays. Lipid metabolism was evaluated by (14)C-oleate incorporated into cholesterol esters as well as by oil red O staining. Moreover, the cultures of pterygium fibroblasts were supplemented with two antiproliferative drugs in order to confirm the effective alterations in cholesterol metabolism related to proliferation. Immunohistochemistry of frozen sections from primary pterygium demonstrated an increased staining in Ki-67 and p53 compared with staining observed in normal conjunctiva. A dramatically increased activity of intracellular cholesterol metabolism was demonstrated in pterygium fibroblasts obtained from four different patients. This finding was confirmed by the reduction of cholesterol metabolism in pterygium fibroblasts treated with antiproliferative drugs. Collectively, these data support the hypothesis that alterations of cholesterol metabolism are involved in the development of pterygia. This finding may represent a target of new therapeutic approaches for treatment and prevention of pterygium.
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PMID:Fibroblasts isolated from human pterygia exhibit altered lipid metabolism characteristics. 1669 71


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