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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The p53 tumour suppressor gene is activated following cellular exposure to DNA-damaging agents. The functions of wild-type p53 protein include transient blocking of cell cycle progression, direct or indirect stimulation of DNA repair machinery and triggering of apoptosis if DNA repair fails. Therefore, the status of p53 protein may be critically associated with tumour cell radiosensitivity. In the present study we examine the intrinsic radiosensitivity of 20 human carcinoma cell lines derived from 15 patients with different types of head and neck tumour. Radiosensitivities were measured in a 96-well plate clonogenic assay in terms of the mean inactivation dose, surviving fraction at 2 Gy, and constants alpha and beta in the linear quadratic survival curve. The p53 allele status was determined by amplifying exons 4-10 by the polymerase chain reaction (PCR), screening for mutations using single-strand conformation polymorphism (SSCP) analysis and determining the exact type and location of a mutation by direct sequencing. The results showed that prevalence of p53 mutations in squamous cell carcinoma (SCC) cell lines is high (80%), and that deletion of one or both wild-type alleles is common (75%). Intrinsic radiosensitivity of the cell lines varied greatly in terms of mean inactivation dose, from 1.4 +/- 0.1 to 2.6 +/- 0.2 Gy. Radiosensitivity correlated well with the p53 allele status so that cell lines carrying a wild-type p53 allele were significantly (P < 0.01) more radioresistant (mean inactivation dose 2.23 +/- 0.15 Gy) than cell lines which lacked a wild-type gene (1.82 +/- 0.24 Gy). Evaluation of our own results and those published in the literature lead us to conclude that absence of the wild-type p53 allele in human head and neck cancer cell lines is associated with increased radiosensitivity. However, the sensitivity is also strongly dependent on the exact type and location of the p53 mutation.
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PMID:p53 mutations associated with increased sensitivity to ionizing radiation in human head and neck cancer cell lines. 878 85

The aim of this study was to investigate bcl-2 expression in head and neck cancer patients and to investigate its correlation with biological and clinical characteristics and outcome of accelerated radiotherapy. A series of 93 patients with squamous cell carcinoma of the head and neck who had been uniformly treated with continuous hyperfractionated accelerated radiation treatment (CHART) were investigated. These patients had also been injected with bromodeoxyuridine (BrdUrd) to measure cell kinetic parameters using flow cytometry (FCM) and their p53 protein status had also previously been described. Bcl-2 expression was assessed using immunohistochemistry. Sixteen of the 93 (17.2%) patients stained positively for bcl-2 proto-oncogene. The percentage of positive tumour cells within the specimens was highly variable, ranging from a few percent to complete positivity. Bcl-2 positivity was correlated with improved local control (p > 0.0016) and survival (p > 0.012) in comparison with non-expressing tumours. There was no correlation between bcl-2 expression and histological grade, T stage or site but overexpressors were almost exclusively node negative. The significance of bcl-2 was reduced when node negative tumours were analysed alone. There was no correlation of bcl-2 with p53 expression but there was a trend for overexpression to be associated with diploidy and rapidly proliferating tumours. These data suggest that bcl-2 expression in head and neck cancer is not associated with disease progression.
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PMID:Bcl-2 expression correlates with favourable outcome in head and neck cancer treated by accelerated radiotherapy. 881 42

Wild-type (wt) p53 DNA was transfected into the radioresistant human cell line JSQ-3, established from a squamous cell carcinoma of the head and neck (SCCHN), using a transferrin-liposome system, and the ability of the introduced wt p53 to sensitize the transfected JSQ-3 cells to ionizing radiation was examined. Transferrin increased the in vitro transfection efficiency of cationic liposomes up to 70-80% in JSQ-3 cells, representing a 6- to 10-fold increase over liposome transfection alone. The exogenous wt p53 was expressed at high levels in transferrin-liposome-DNA-transfected cells and resulted in the reversion of the radioresistant phenotype of the JSQ-3 cells in a DNA dose-dependent manner. The D10 values were reduced from 6.36 +/- 0.54 Gy to 4.13 +/- 0.06 Gy, a value in the radiosensitive range. In vivo, the intratumoral injection of the transferrin-liposome system resulted in a higher number of transfected tumor cells in the JSQ-3 induced nude mouse xenografts when compared with transfection by liposome alone. The results indicate that the combination of p53 replacement gene transduction, mediated by the relatively safe transferrin-liposome system, and conventional ionizing radiation may provide a more effective treatment for head and neck cancer.
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PMID:Transferrin-liposome-mediated p53 sensitization of squamous cell carcinoma of the head and neck to radiation in vitro. 905 21

p53 mutations are amongst the most prevalent alterations in human cancer. Overexpression of p53 is usually caused by mutation and is observed in a high percentage of squamous cell carcinomas of the head and neck (SCCHN). Fifty two fresh samples of SCCHN were examined for p53 overexpression and 23 tumor-free tonsils served as controls. Using the monoclonal antibody Pab 1801 a refined ELISA technique was employed. In contrast to established ELISA procedures tumor tissue was pulverized at -80 degrees C prior to the actual ELISA (ELISA I). Comparative p53 detection was carried out by immunohistochemistry (IHC) and a commercially available ELISA kit (ELISA II). The modified ELISA I revealed p53 overexpression in 48 tumor samples (92%). p53 detection was obtained in 26 cases (50%) with ELISA II and with IHC 39 stained positive for p53 (75%). All of the controls were negative for p53 with ELISA and IHC. The p53 staining in IHC showed a significant correlation with the grading of the tumor. The ELISA results of the p53 overexpression did not show any correlation with tumor size or stage and rate of metastasis or other clinical parameters. This ELISA represents a more sensitive detection method of p53 than any other technique so far. It improves on former ELISA and IHC results on p53 overexpression in squamous cell carcinoma of the head and neck and underlines the involvement and the importance of the p53 tumor suppressor protein in carcinogenesis of head and neck cancer.
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PMID:High rate of p53 overexpression in head and neck carcinomas detected with a refined ELISA. 906 97

Malignant transformation and tumor progression are currently thought to be the result of the accumulation of genetic alterations in critical genes, the proto-oncogenes and the tumor suppressor genes. Among the tumor suppressor genes, the p53 tumor suppressor gene mutations are the most prevalent. In order to determine genetic instability and p53 expression, we analyzed the genetic changes of chromosome 9 and 17 by non-isotopic in situ hybridization in formalin-fixed, paraffin embedded tissues and calculated for normalized chromosome index (NCI) and polysomy index (PI), and the expression of p53 by using immunohistochemistry (IHC). The means of chromosome 9 and 17 NCI were found to increase gradually as the tissues progressed from normal to squamous cell carcinoma; 1.02 and 1.03, respectively, in normal adjacent tissue (ANL), 1.19 and 1.20 in hyperplasia (HYP), 1.28 and 1.31 in mild dysplasia (MD), 1.38 and 1.43 in moderate dysplasia (ModD), 1.39 and 1.66 in severe dysplasia/carcinoma in situ (SD/CIS), and 1.65 and 1.83 in squamous cell carcinoma (SCC). Moreover, the PI 9 and 17 means also increased as the tissues passed from histologically normal epithelium to HYP to dysplasia (DYP) to cancer. In ANL, PI 9 and 17 means were 0.90 and 1.53 percent, compared to 3.78 and 3.38 percent in HYP, 3.73 and 5.12 percent in MD, 5.66 and 8.47 percent in ModD, 13.56 and 20.99 percent in SD/CIS, and 17.74 and 22.50 percent in SCC. Interestingly, p53 expression also increased continuously, not only in amount but also in the incidence of its expression, as the tissues progressed from normal to cancer, 2.29 percent in ANL, 4.65 percent in HYP, 9.09 per cent in MD, 9.58 per cent in ModD, 29 percent in SD/CIS, and 38.67 per cent in SCC in the amount; and 3 of 33 (9%) in ANL, 6 of 37 (16%) in HYP, 5 of 21 (24%) in MD, 3 of 12 (25%) in ModD, 8 of 18 (44%) in SD/CIS, and 24 of 49 (49%) in SCC in the incidence. Our studies demonstrated that genetic instability and p35 expression occurred very early from ANL to SCC and increased gradually through HYP, DYP, to SCC in head and neck cancer. The genetic instability and the loss of normal p53 function play the potential role in multistep tumorigenesis in head and neck cancer and might be the useful biomarkers in assessing the risk of tumor development.
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PMID:Genetic instabilities of chromosome 9, 17 and accumulation of p53 overexpression during multistage tumorigesis in head and neck cancer. 907 Oct 74

This study looks at p53 protein expression in dysplastic and malignant lesions of the oral cavity using an immunohistochemical staining technique. Archival biopsy specimens of oral dysplasia of squamous cell carcinoma from 64 patients were analysed immunohistochemically. Sections from 90 oral biopsy specimens were examined in all. Positive immunohistochemical detection of the p53 protein, demonstrated by brown nuclear staining, was detectable in over 80% of mild, moderate and severe dysplastic tissues as well as carcinoma-in-situ and squamous carcinoma specimens. We concluded that p53 protein expression occurs frequently in both malignant and dysplastic lesions of the oral cavity, suggesting that abnormally detectable p53 protein is present at the very early stages of development of oral squamous carcinoma. Oral cancer may provide a good model for the study of multistage tumorigenesis in head and neck cancer as the lesions are frequently detected at the pre-invasive stage and are accessible to biopsy.
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PMID:An immunohistochemical analysis of p53 protein expression in pre-malignant and malignant tissues of the oral cavity. 908 74

p53 antibodies are a new serological parameter of unknown potential in patients with malignancies. Their occurrence has been described in various types of cancer patients. The mechanism underlying the immunization process is still unclear. We investigated the incidence of p53 serum antibodies in 143 head and neck cancer patients with an enzyme-linked immunosorbent assay. The posttherapy course of two matched study groups (n = 38 each), one p53-antibody-seropositive and one p53-antibody-seronegative, was followed up for 24 months. Thirty-nine head and neck cancer patients (27.3%) were seropositive for p53 antibodies. During the follow-up, the p53-antibody-seropositive patients accounted for more local tumor recurrences (n = 12 versus n = 8) and more tumor-related deaths (n = 11 versus n = 5) than did seronegative patients, and second primary tumors (n = 9 versus n = 0) occurred exclusively in seropositive patients. In total, therapy failures (recurrences, tumor-related deaths, second primaries) were observed in 17/38 cases (44.7%) in the p53-antibody-seropositive group and in 8/38 cases (21.1%) in the p53-antibody-seronegative group. These results, after a follow-up of 2 years, seem to indicate a prognostic value of p53 serum antibodies for therapy failure in patients with head and neck cancer.
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PMID:p53 serum antibodies as prognostic indicator in head and neck cancer. 917 73

We investigated the p53 expression and the presence of HPV DNA in 90 patients with squamous cell carcinomas (SCCs) of the head and neck and the relation to clinicopathological parameters and patients' prognosis. Immunohistochemical analysis of p53 protein was conducted by using monoclonal anti-p53 antibody, clone 1801 and clone 240. The relationship between the overexpression of p53 and the duration of survival of patients was analyzed. The polymerase chain reaction (PCR) was carried out with consensus primers capable of detecting HPV16, 18, 31, 33, 52b and 58. In situ hybridization was performed in the mesopharyngeal carcinoma to confirm the presence of HPV genomes in cancer cells with a wide-spectrum cDNA probe capable of detecting HPV6, 11, 16, 18, 30, 31, 33, 35, 45, 51, 52. Forty-five tissue samples (50%) were immunohistochemically positive for p53. T-category, N-category, primary site of tumor, clinical stage and tumor differentiation did not correlate with p53 expression. Our finding that p53 overexpression occurred in 50% of head and neck tumor samples is similar to the frequency of p53 overexpression reported for both lung and esophageal cancer. The common risk factor is the same in these neoplasms, and therefore it is not surprising to find a similar percentage of p53 overexpression. The prevalence of metastasis was higher in the patients with p53-positive staining than in those with p53-negative staining (p < 0.10). Analysis of cumulative survival rates of patients by the Kaplan-Meier method showed a close correlation between p53 expression and survival time. The survival differences according to p53 immunostaining were significant (p 0.05). Our results indicate that p53 immunohistochemical evaluation may be useful as one of the new prognostic parameters in head and neck cancer patients. The HPV genomes were detected in 9 of 90 patients (10.0%); 8 of 9 patients with mesopharyngeal cancer and one with maxillary cancer, namely, 29.6% of mesopharyngeal cancers and 6.7% of maxillary cancer contained HPV DNA sequences. Seven of 8 patients had SCCs of tonsil origin. Almost all of the HPV infections in our study occurred in patients with mesopharyngeal cancer, and it has been suggested that this anatomic subsite may be more frequently infected by HPV than other sites within the head and neck region. Among the 27 patients with mesopharyngeal cancer, HPV DNA-positive patients experienced a higher incidence of complete remission than HPV DNA-negative patients (87.5% vs. 26.3%, p < 0.05).
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PMID:[Detection of human papilloma virus DNA and expression of p53 protein in patients with head and neck cancer]. 918 31

Molecular genetics has led to new insights into diagnosis and treatment of human cancer. The alterations of tumor suppressor genes like retinoblastoma, p53 and others may have an important role in tumorigenesis. Mutations of p53 have been found in a majority of human malignancies including head and neck cancer. The distribution of p53 is different between types of tumors, suggesting environmental exposure as a cause active factor. The p53 mutation in head and neck tumors is an early event and appears to have a hot spot region at codons 238-248. While mutation and loss of heterozygosity at p53 are important in the genesis of head and neck cancer, other mechanisms such as binding of viral and cellular proteins to p53 are also likely to play a role.
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PMID:The role of p53 tumor suppressor gene in human head and neck tumorigenesis. 919 75

Recent reports of p53 positivity in the normal mucosa of some head and neck cancer patients have been taken as evidence for field cancerization and hence a likelihood of the development of further tumours, yet few papers report the clinical significance of this finding through long-term follow-up. The immunohistochemical detection of p53 expression in clinically and histopathologically normal oral mucosa taken from the wound margin following excision of oral cancer was assessed using the polyclonal antibody CM1. Fresh frozen biopsies of normal oral mucosa and the corresponding tumour from 21 oral cancer patients and of normal mucosa from 25 non-cancer patients were assessed for p53 overexpression. The 'normal' mucosa was positive in 12 of the oral cancer patients and one of the non-cancer patients. Second malignant tumours were seen in patients from whom p53-positive 'normals' and p53-negative 'normals' were recorded. In five of the p53-positive 'normals', the corresponding cancer was p53-negative. In one case, where 'normal' mucosa was available from more than one site, one region was positive, whilst the other was negative. No obvious difference in age, tobacco use, or recurrence rate was seen between positive and negative cases. All patients who were still alive were reviewed for a minimum of 5 years. Using Fisher's exact test, no statistically significant difference was found for the rate of second malignant tumours occurring in patients with p53-positive compared with p53-negative normal mucosa. Thus, the detection of p53 in normal mucosa did not necessarily predict a further tumour.
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PMID:Overexpression of p53 in normal oral mucosa of oral cancer patients does not necessarily predict further malignant disease. 927 28


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