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)

Thymidine phosphorylase (TP) has been implicated as a potent angiogenic factor and a prognostic factor in various human solid tumors. We investigated the expression of TP in a series of human astrocytic tumors using immunohistochemistry, enzyme-linked immunosorbent assay, and reverse transcriptase/polymerase chain reaction (RT-PCR) analysis. A total of 63 astrocytic tumors [27 glioblastomas (GBM), 19 anaplastic astrocytomas (AA), 17 low-grade astrocytomas (LGA)] and 5 normal brain tissues were immunohistochemically stained with antibodies to TP, vascular endothelial growth factor (VEGF), p53, MIB-1, and factor-VIII-related antigen. They were also evaluated for the degree of apoptosis by a ApopTag kit. Ten tumors (5 GBM, 2 AA, 3 LGA) and 3 normal brain tissues were evaluated for their expression of VEGF and TP by RT-PCR analysis. TP was constantly localized in the cytoplasm of astrocytic tumor cells, less intensely in the cytoplasm of vascular endothelial cells, but not in the normal brain. Some of the TP-positive cells were of macrophage origin, but most positive cells were the tumor cells themselves. Vascular density, MIB-1 positivity, p53 positivity, VEGF expression, and the apoptotic index were significantly higher in the TP-positive tumors than in TP-negative tumors. There was a significant correlation between TP and VEGF mRNA expression. In a limited number of glioblastoma cases, the apoptotic index was significantly higher in TP-positive glioblastomas than in TP-negative glioblastomas. In human astrocytic tumors, TP was expressed in the tumor, macrophage, and endothelial cells. TP was a potent angiogenic factor closely associated with cell proliferation and tumor apoptosis.
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PMID:Expression of the angiogenic factor thymidine phosphorylase in human astrocytic tumors. 1074 8

Antitumor effect of N-9-[2-(phosphonomethoxy) ethyl]-2,6-diaminopurine (PMEDAP) was studied in an in vivo model of s.c. transplanted Sprague-Dawley (SD/cub) rat T-cell lymphomas. Three individual SD/cub neoplasias (SD10/96, SD14/97, SD1/90) of different phenotypes were used. During the treatment, survival of the rats, increase of lymphoma mass, and DNA fragmentation detected by APO/BRDU kit, as well as Bcl2 and p53 protein expression, were followed. The study gives evidence of the positive therapeutic effect of PMEDAP in two of the three tested lymphomas, SD10/96 and SD14/97. Slowly growing SD1/90 lymphoma differs from the others in a uniform karyotype with trisomy of chromosome 11, CD4- immunophenotype, heterogeneous cellular morphology and constitutive expression of p53 protein found in some neoplastic cells. Thus, the diverse anticancer efficacy of PMEDAP treatment among SD/cub lymphomas could be associated with the different phenotypes of individual neoplasias.
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PMID:Anticancer effect of PMEDAP--monitoring of apoptosis. 1081 Mar 95

Alteration of the p53 gene product occurs frequently during the progression of colorectal cancer. Recently, mutated p53 protein was found to induce the production of anti-p53 antibodies in the serum of patients. The purpose of this study was to evaluate the relationship between p53 status in serum and chemosensitivity in resectable colorectal cancer patients. A total of 35 patients with primary colorectal cancer who underwent surgical treatment were examined by chemosensitivity test with the viable tumor samples using Histoculture Drug Response Assay (HDRA). Serum samples of these patients to test for p53 antibodies were obtained before tumor resection, and assayed in duplicate by using an enzyme-linked immunosorbent assay (ELISA) kit. The inhibition index of 5-FU and CDDP, determined by the HDRA method, in the sero-positive group was significantly lower than that of the sero-negative group (p < 0.01). Furthermore, significant statistical differences in chemosensitivity to 5-FU and CDDP were revealed depending on the presence of serum p53 antibodies. There was no relationship between chemosensitivity assay and tumor marker positivity or clinicopathological features in these patients. Detection of serum p53 antibodies, which reflects p53 mutations in tumor tissue, is a simple method which correlates with chemosensitivity, and may contribute to the selection of favorable chemotherapeutic strategies of colorectal cancer.
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PMID:[Clinical significance of serum p53 antibody detection in a chemosensitivity assay in cases of human colorectal cancer]. 1089 15

Prognostic relevance of serum p53 antibodies was assessed in 96 patients with microscopically proven small cell lung cancer (SCLC). The study group included 67 males and 29 females; mean age 58 years; range 35--86 years; 60 with limited disease (LD), and 36 with extensive disease (ED). The control group consisted of 41 patients with non-malignant diseases. The presence of p53 antibodies was assayed by the immunoenzymatic method (P53 ELISA kit, PharmaCell, France). Antibodies were present in 26 SCLC cases (27%); 15 (25%) in LD and 11 (31%) in ED. Antibodies were also found in one out of 41 control subjects (2%). There was no correlation between the level of antibodies and clinical characteristics of SCLC patients including age, gender and extent of disease. The median follow-up for the entire group was 30 months (range: 11--39 months). By the time of analysis, 78 patients (82%) had deceased. Median survival in SCLC patients with and without antibodies was 42 and 39 weeks, respectively (log rank, P=0.81). These results indicate the lack of clinical relevance of serum p53 antibodies in SCLC.
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PMID:Serum p53 antibodies in small cell lung cancer: the lack of prognostic relevance. 1116 62

Evaluation of the biology of laryngeal cancer cell is connected either with many process inside the cell or reactions between cancer cell itself and extracellular matrix. The main purpose in this paper was the evaluation of p53 protein, bcl-2 protein, Ki-67 antigen and CD44 adhesive molecule expressions in comparison to clinical and histopathological features in patients with laryngeal cancer. Paraffin-embedded tissue sections from 89 patients with laryngeal cancer were stained with a monoclonal antibody raised against p53 and bcl-2 proteins, Ki-67 and CD44 antigens using a peroxidase-labelled streptavidin-biotin kit. There were statistically significant relationships between p-53 protein over-expression and pT, histological grading, survival and Ki-67 and CD44 antigens expressions. There were no correlation between bcl-2 protein expression and clinical and histopathological features. We observed statistically significant correlation between Ki-67 expression and pT, histological grading, recurrences and survival. Expression of CD44 statistically significant correlated only with tumour size. We conclude that comparison of data covering mentioned tumour markers expression gives valuable evaluation of biological activity of cancer cells and may allow to create the immunological panel of tumour markers which simplify the prognosis about nodal metastases, recurrences and survival in patients with laryngeal cancer.
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PMID:[Expression of selected markers for apoptosis, proliferation and metastasis in evaluation of laryngeal cancer invasiveness dynamics]. 1126 75

The aim of the present study was to evaluate the clinical significance of the serum anti-p53 antibody in patients with uterine and ovarian cancer. Some of the ovarian patients were also evaluated for overexpression of p53 by immunohistochemistry and for cytogenetic alterations by comparative genomic hybridization (CGH). Serum anti-p53 antibodies were determined by an enzyme immunoassay kit. The antibody was detected in 8/30 (27%) of ovarian cancers, in 12/86 (14%) cancers of the uterine cervix, in 5/41 (12%) cancers of the uterine body, and 0/9 (0%) healthy women. The overall survival rate in patients with ovarian cancer was significantly worse in patients with anti-p53 antibody positivity than that in patients with anti-p53-antibody-negative cancers using the log rank test (p = 0.017). There was a significant correlation between the presence of anti-p53 antibody and tissue overexpression of p53 in ovarian cancers. CGH analysis showed that the aberrations in DNA sequence copy number in ovarian cancers were significantly increased in anti-p53-antibody-positive cases compared to antip53-antibody-negative cases including increased copy number on 20q and reduced copy number on 5q and 13q. Although the exact relationship between the presence of serum anti-p53 antibody (specific humoral response) and cytogenetic alterations is still unknown, these findings suggest that the measurement of serum anti-p53 antibody may be useful for the assessment of genetic instability and tumor biological aggressiveness.
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PMID:Serum anti-p53 antibodies in uterine and ovarian cancer: association with dna sequence copy number abnormalities. 1127 94

We examined, immunohistochemically and molecular biologically, p53 gene expression in 10 patients with colonic cancer. RNA was extracted from paraffin embedded normal and colonic cancer tissues by using RNA isolator kit and proteinase K. The most effective time and concentration of proteinase K for RNA extraction was 24 hours and 100 micrograms/ml, respectively. P53 gene expression was analyzed by ABI PRISM 7700 Sequence Detection System(ABI 7700 System, Perkinelmer). Gene expression level in each sample was estimated on the basis of the standard curve of ABI 7700 System. Human G3PDH gene was used as the internal control. Immunohistochemically, the tumor cells in all examined cases showed a strong positivity for anti-p53 gene antibody. In ABI 7700 System, expression of p53 gene in the malignant tissues revealed a high level in only 2 cases that had a clinical stage IV, however, in remaining 8 cases a clinical stage was I to III and expression level of p53 was relatively lower. These results suggest that colonic cancer cells show mutant-p53 gene expression, and a ratio of mutant- to wild-p53 gene may have something to do with a relationship between gene expression and clinical stage.
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PMID:[Extraction of RNA from paraffin embedded tissues and analysis of p53 gene expression in colonic cancer]. 1130 29

Mutations of the p53 gene have been reported to be of prognostic significance in hepatocellular carcinoma (HCC). However, the clinical associations and prognostic value of anti-p53 antibodies, known to be products of the host immune response to these mutations, have been controversial. Serum anti-p53 antibodies were measured in 121 Thai patients diagnosed with HCC using a specific enzyme-linked immunosorbent assay (ELISA) kit. The clinical/pathological characteristics of the patients were compared with respect to the presence of serum anti-p53 antibodies. Cox regression analysis was performed to assess factor interaction and association with survival. Anti-p53 antibodies were detected in 13.2% (16 of 121) of our patients. There were no differences between groups with regard to age, sex, viral markers (HBsAg or anti-HCV), severity of liver disease and tumor advancement. The median survival rates for patients positive and negative for anti-p53 antibodies were 4.0 and 3.0 months, respectively (p = 0.443, by log-rank test). Multivariate analysis demonstrated that an advanced Okuda stage, lack of therapy and presence of portal vein thrombosis were independent factors related to the prognosis of the patients. Nonetheless, the presence of anti-p53 antibodies did not constitute a predictive variable associated with a poorer prognosis. Serum assay of anti-p53 antibodies, although rapid and easily performed, may not be suitable as an alternative to molecular detection of mutations in assessing tumor advancement and prognosis of patients with HCC.
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PMID:Clinical associations and prognostic significance of serum anti-p53 antibodies in Thai patients with hepatocellular carcinoma. 1131 45

We evaluated p53 autoantibodies (p53-Ab) as a preoperative tumor marker and as a prognosis marker. We also investigated whether p53-Ab production is dependent on p53 protein overexpression in tumor tissue or on tumor volume. Serum samples of patients with a colorectal cancer (n = 130) and of healthy controls (n = 44) were examined for p53-Ab using an ELISA kit. P53 protein expression in tumor tissue was demonstrated immunohistochemically and quantified by ELISA. Tumor volume was calculated and patients' survival computed using the Kaplan-Meier method. p53-Ab were detected in the serum from 15% of patients; all controls were negative. There was a significant correlation between p53-Ab production and positive immunostaining or p53 protein concentration in tumor tissue. p53-Ab were detected at a higher percentage of patients with a tumor volume of 10 cm3 or greater than in those with a smaller tumor. No difference in patients' prognosis was found between the p53-Ab positive and negative groups. Because of their low sensitivity (15%) p53-Ab are not suitable as a preoperative tumor marker. However, their high specificity (100%) and their potential for early diagnosis of a tumor relapse makes them valuable for postoperative monitoring during follow-up in p53-Ab positive patients. Furthermore, their detection can be used as a simple serological test for early detection of p53 alterations.
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PMID:p53 autoantibodies in sera of patients with a colorectal cancer and their association to p53 protein concentration and p53 immunohistochemistry in tumor tissue. 1131 93

Cr (VI) compounds are widely used industrial chemicals and are recognized human carcinogens. The mechanisms of carcinogenesis associated with these compounds remain to be investigated. The present study focused on dose-dependence of Cr (VI)-induced uptake and cellular responses. The results show that Cr (VI) is able to enter the cells (human lung epithelial cell line A549) at low concentration (< 10 microM) and that the Cr (VI) uptake appears to be a combination of saturable transport and passive diffusion. Electron spin resonance (ESR) trapping measurements showed that upon stimulation with Cr (VI), A549 cells were able to generate reactive oxygen species (ROS). The amount of ROS generated depended on the Cr (VI) concentration. ROS generation involved NADPH-dependent flavoenzymes. Cr (VI) affected the following cellular parameters in a dose-dependent manner, (a) activation of nuclear transcription factors NF-kappaB, and p53, (b) DNA damage, (c) induction of cell apoptosis, and (d) inhibition of cell proliferation. The activation of transcription factors was assessed by electrophoretic mobility shift assay and western blot analysis, DNA damage by single cell gel electrophoresis assay, cell apoptosis by DNA fragmentation assay, and cell proliferation by a non-radioactive ELISA kit. At the concentration range used in the present study, no thresholds were found in all of these cell responses to Cr (VI). The results may guide further research to better understand and evaluate the risk of Cr (VI)-induced carcinogenesis at low levels of exposure.
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PMID:On the mechanism of Cr (VI)-induced carcinogenesis: dose dependence of uptake and cellular responses. 1167 6


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