Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Esophageal carcinomas from 24 patients, most of whom were smokers and consumed alcoholic beverages daily, were analyzed for mutations in exons 5-8 of the p53 tumor suppressor gene. Mutations were identified by polymerase chain reaction amplification and direct sequencing in 12 of 24 (50%) of the samples; almost half of the mutations were at A:T base pairs. Nuclear accumulation of p53 protein, determined by immunohistochemistry with the CM-1 polyclonal antibody, was observed in all cases in which a missense mutation in the p53 gene was detected. None of the 24 carcinomas had amplification of the mdm2 gene, an alternate pathway to p53 loss of function. Alterations involving three other cancer-related genes associated with human esophageal carcinogenesis, c-erbB-1/epidermal growth factor receptor (EGFR), c-myc, and retinoblastoma (Rb), were examined by Southern blot or immunohistochemical analysis in the same sample set to explore the possibility of a link between oncogene activation and loss of tumor suppressor function. While no associations were observed between amplification of the c-myc or EGFR genes and p53 abnormalities, a significant correlation (P < 0.01) was seen between the presence of p53 mutation and EGFR overexpression. Absence of Rb protein, measured immunohistochemically, was observed in four tumors, none of which had aberrations of the p53 gene.
 ...
PMID:Correlation of p53 mutations with epidermal growth factor receptor overexpression and absence of mdm2 amplification in human esophageal carcinomas. 828 Mar 79

Oesophageal epithelium is frequently exposed to various carcinogens and mutagens, many of which may cause p53 gene mutations. The epithelium can also be infected with human papillomavirus (HPV), the E6 protein of which may complex with p53 protein and facilitate its degradation. To identify HPV infection and p53 overexpression in oesophageal cancer, we performed immunohistochemical analysis using CM-1 anti-p53 antibody and DNA in situ hybridization with biotinylated HPV DNA probes on paraffin-embedded sections in 36 patients with oesophageal squamous cell carcinomas derived from a high-incidence area in northern China. Samples from cancer tissue, adjacent epithelia, regional lymph nodes as well as resection margins were examined. p53 protein accumulation was detected in 55.6% (20/36) of cancer samples, in 20% (1/5) of hyperplastic epithelium, in 20% (2/10) of dysplastic lesions as well as in 67% (2/3) of carcinoma in situ lesions adjacent to invasive carcinomas. HPV DNA sequences were demonstrated in 3 patients (8.3% of the total). Two of these HPV-positive carcinomas were immunohistochemically negative for p53 and one was weakly positive. Our results suggest that p53 overexpression is frequently found in oesophageal carcinomas and that p53 alteration may be an early event in esophageal carcinogenesis. HPV and elevated p53 are not mutually exclusive events, instead they can coexist in some oesophageal squamous cell carcinomas.
 ...
PMID:p53 overexpression and human papillomavirus (HPV) infection in oesophageal squamous cell carcinomas derived from a high-incidence area in China. 906 6

Dietary zinc deficiency in rats induces hyperplasia in the esophagus and increases N-nitrosomethylbenzylamine (NMBA)-induced esophageal tumor incidence. Previous work showed a direct relationship between epithelial cell proliferation and esophageal tumor incidence in rats given multiple doses of NMBA. We investigated the effects of single low doses of NMBA in zinc-deficient rats since a single dose of 5.0 mg/kg was reported to be non-carcinogenic in rats. Zinc-sufficient and deficient rats received a single i.g. dose of NMBA at 0.5 or 2.0 mg/kg. At week 14, tumor incidence was 50% with 0.8 +/- 1.0 tumors/rat, and 80% with 2.2 +/- 1.9 tumors/rat, in deficient groups, D(0.5) and D(2.0), that received the lower and higher dose, respectively. In addition, two small papillomas were found in one out of eight untreated zinc-deficient rats. None of the NMBA-treated or untreated zinc-sufficient rats had any tumors. Esophageal cell proliferation, as determined by proliferating cell nuclear antigen (PCNA) immunohistochemistry, showed that, irrespective of NMBA treatment, deficient esophagi had significant increases in the number of labeled cells, the total number of cells, and the labeling index, as compared with zinc-sufficient ones. Mutations in Ha-ras and p53 genes in esophageal tumors were detected by single strand conformation polymorphism (SSCP) analysis. DNA sequencing of variant conformers revealed a point mutation (GGA-->GAA, codon 12) in Ha-ras in 4/5 (80%) and 5/8 (63%) tumors, from D(0.5) and D(2.0) rats, respectively. Three out of eight tumors from D(2.0) rats exhibited SSCP mobility shifts within p53 exons 5 and 7: two tumors (2/8, 25%) had missense mutations and the third, a silent mutation. Of the two tumors with p53 mutations, one had a double mutation (transition at codon 164, TCA-->TTA; transversion at codon 241, AGT-->TGT), and the other tumor, a transition at codon 172 (AGA-->GGA), with amino acid changes in all cases. In parallel with PCNA expression, elevated p53 expression was associated with hyperplastic and dysplastic regions, as well as with tumors, in deficient esophagi. In short, these data indicate that dietary zinc deficiency, with its associated sustained increased cell proliferation in the esophagus, can drive an otherwise non-tumorigenic dose of NMBA into a highly tumorigenic one.
 ...
PMID:Induction of esophageal tumors in zinc-deficient rats by single low doses of N-nitrosomethylbenzylamine (NMBA): analysis of cell proliferation, and mutations in H-ras and p53 genes. 927 19

Esophageal tumors from 29 patients residing in Guangzhou, China were examined for mutations in exons 5-8 of the p53 tumor suppressor gene and for p53 protein accumulation in tumor cell nuclei. Anamnestic data for each patient, which included information on family history of cancer, tobacco smoking, drinking of alcoholic beverages, and dietary habits such as consumption of pickled vegetables, were recorded. Screening of DNA from tumor cells microdissected from biopsies was performed by PCR amplification of p53 gene exons 5-8, denaturing gradient gel electrophoresis analysis, and DNA sequencing. Mutations were identified in 20 of 29 tumors (69%). All tumors harboring a missense mutation in the p53 gene also showed nuclear accumulation of the tumor suppressor protein by immunohistochemistry. The most common p53 mutations in these tumors were guanine to adenine (G-->A) transitions (10 of 20 tumors; 50%). We did not find multiple mutations at codon 176, in contrast to Lung et al. in their recent study of esophageal cancer patients from Guangzhou (M. L. Lung et al., Cancer Epidemiol. Biomark. Prev., 5: 277-284, 1996). The mutation prevalence was high both in smokers (13 mutations in 20 smokers; 65%) and in nonsmokers (7 of 9 tumors with mutations; 78%), an observation that differs from that of studies in European and North American patients, which demonstrate a much higher prevalence of p53 mutations in smokers than in nonsmokers (reviewed in R. Montesano et al., Int. J. Cancer Predict. Oncol., 69: 225-235, 1996.). Our findings in this pilot study of tumor suppressor gene mutations in patients from Guangzhou support a large body of epidemiological observations pointing to dietary mutagenic carcinogens peculiar to populations in China at high risk of esophageal cancer.
 ...
PMID:p53 mutations in esophageal tumors from a high incidence area of China in relation to patient diet and smoking history. 936 71

Esophageal squamous cell carcinoma (ESCC) demonstrates wide regional variation in incidence and causal associations. Human papillomavirus (HPV) has been implicated in ESCC, particularly the sub-types 16 and 18. Transforming proteins E6 and E7 from these high risk sub-types, interact with p53 protein and Rb protein respectively, leading to loss of function of these tumor suppressor gene products. These interactions further lead to inactivation of the growth suppressive effects of the p53 and Rb proteins, resulting in abnormal proliferative states. p53 protein expression has been found in both HPV-positive and -negative tumors, indicating that HPV and p53 protein expression are not mutually exclusive and can occur together in the same tumor. It has been observed that HPV plays a more significant role in esophageal carcinogenesis in geographic areas with a high prevalence of the disease. A variation in the association between HPV and ESCC worldwide may be due to environmental and geographic factors, or to genetic susceptibility to esophageal HPV infections. Variations in the sensitivity of techniques used in the detection of the virus and in the methodology for processing the tumor tissues, may also be responsible for global differences. Esophageal carcinogenesis is a complex multistep process with a multifactorial etiology. Infection with oncogenic HPV types may be an integral part in a multistep process that leads to ESCC.
 ...
PMID:The role of the human papilloma virus in esophageal cancer. 983 8

The present study was undertaken in order to investigate the possible involvement of high-risk human papillomavirus (HPV; types 16 and 18) or the overexpression of p53 protein in 123 Japanese patients with esophageal squamous cell carcinoma (SCC) from five different institutions. We detected HPV DNA in 30.1% (37/123) by in situ hybridization (ISH). Of these 123 cases, HPV type 16 was detected in 22 cases and HPV type 18 in 23 cases. In addition, HPV types 16 and 18 were detected simultaneously in eight cases. We found an almost similar incidence of HPV infection at five different places in Japan. Then, among these patients, 24 fresh tumor samples were also examined for screening the presence of HPV DNA using dot blot hybridization (DBH) and polymerase chain reaction (PCR). We detected HPV DNA in 20.8% (5/24) by DBH and in 12.5% (3/24) by PCR. P53 protein overexpression was found in 34.1% (43/123) by immunohistochemistry (IHC). Furthermore, in 43 cases from Kochi Medical School, the group positive for p53 antibody statistically showed worse survival rate than the group negative for both HPV DNA and p53 antibody. Judging from these results obtained in the present study, HPV infection and p53 overexpression are frequently detected and involved in the carcinogenesis of esophageal SCC in Japan. We also found that no significant geographical difference of both HPV infection and p53 overexpression of esophageal SCC was seemingly present in Japan.
Dis Esophagus 1998 Jul
PMID:High-risk human papillomavirus infection and overexpression of p53 protein in squamous cell carcinoma of the esophagus from Japan. 984 97

We generally choose transhiatal esophagectomy (THE) for patients with high risk for postoperative complications and for carcinoma of the lower thoracic esophagus, even if the tumor is in the advanced stage. In order to define indications for THE in esophageal cancer patients, we investigated 40 THE cancer patients according to the expressions of EGF/EGFR, p53 and p21. In patients with stage I, II, III and IV tumors, 5-year survival rates were 66.7%, 28.6%, 30.0% and 11.4%, respectively. The sites of first recurrence were the lymph nodes (n = 10) and single organs (n = 10). Dissemination (n = 3) and local recurrence (n = 2) were also seen as a first recurrence. According to EGF/EGFR, 5-year survival rate was 69% and 14% in the low and high EGF/EGFR groups, respectively. According to p53 expression, 5-year survival was 60% and 30% in the negative and positive groups, respectively; according to p21 expression, 5-year survival was 71% and 0% in the negative and positive groups, respectively. Significant difference was seen in EGF/EGFR and p21 groups. These data support less invasive surgery for some patients even for esophageal cancer patients. THE is a less invasive surgery, that also implies fewer curative procedure. Our results also showed that THE alone will be the only curative procedure necessary for some patients. We can determine therapeutic procedures using these new factors, and thus avoid unnecessary excess surgical stress in esophageal cancer patients.
Dis Esophagus 1998 Oct
PMID:Clinical results of transhiatal esophagectomy for carcinoma of the lower thoracic esophagus according to biological markers. 1007 2

For thoracic esophageal cancer, we perform extended three field lymph node dissection, and have achieved nearly 50% of overall 5-year survival. However, patients sometimes develop lymph node recurrences in spite of having no lymph node metastases found by conventional histopathologic examination. In a patient with esophageal squamous cell carcinoma, we sequenced all the p53 cDNA translated regions (exon 2-10) of primary carcinoma, and confirmed one p53 nonsense mutation in exon 10. Then we extracted genomic DNA from 150 surgically dissected lymph nodes from that patient, and performed polymerase chain reaction analysis (PCR-RFLP) to detect the same p53 mutation in the lymph nodes. PCR-RFLP analysis showed the same p53 mutation in six lymph nodes. One node was located along the right recurrent laryngeal nerve, where no positive nodes was identified by conventional histopathologic examination. The p53 mutational diagnosis of metastatic cancer may be useful in detecting minimal residual disease.
Dis Esophagus 1998 Oct
PMID:p53 gene mutation in 150 dissected lymph nodes in a patient with esophageal cancer. 1007 15

Recently, various cell cycle regulators have been investigated as biological markers of malignant potential. These regulators might influence the survival rate and the effect of adjuvant therapies. In this study, we analyzed p53, p21(Waf1/Cip1) and cyclin D1 expression in 64 esophageal cancer patients and the relationship between clinicopathologic parameters and patient survival. The positive expression rate was 48.4%, 42.2% and 43.8% in the p53, p21 and cyclin D1 groups respectively. Multivariant analysis revealed that tumor depth, chemotherapy, p53, p21 and cyclin D1 expression showed significant values. p53- and cyclin D1-negative patients had a worse prognosis. p21-positive patients had a better prognosis. In stage 0, I and II patients, there was a significant difference between p53-positive and -negative, p21-positive and -negative, and cyclin D1-positive and -negative groups. In stage III and IV patients, there was no significant difference between any two groups. However, a significant difference was seen in the p21 group: among patients who received adjuvant chemotherapy, the p21-positive group had a 5-year survival rate of 50% compared with 13.4% in the p21-negative group (not significant).
Dis Esophagus 1999
PMID:p53, p21(Waf1/Cip1) and cyclin D1 protein expression and prognosis in esophageal cancer. 1046 43

The correlation between immunohistochemical detection (IH) of p53 protein and tumor response to preoperative chemotherapy and/or radiotherapy in advanced esophageal squamous cell carcinoma was evaluated. Fifty-six patients with advanced esophageal squamous cell carcinoma were included in the study. All patients were staged and diagnosed microscopically before treatment. Patients were divided into three groups: 17 patients treated with chemotherapy and radiotherapy preoperatively (group I) (cisplatin and 5-fluorouracil, cobalt-60 therapy; total dose 3000 Gy); 19 patients treated with chemotherapy only (group II); and 20 patients who did not receive preoperative therapy (group III). The response of the tumor tissue to preoperative treatment was evaluated macroscopically and microscopically in operated specimens according to the classification: CR, complete response; PR1, major partial response with regression of at least 50% of initial tumor mass; PR2, minor partial response with regression of less than 50% of initial tumor mass. In all 56 patients immunohistochemistry was used to detect anti-p53 antibody (Dako, DO-7) in normal mucosa and cancer tissue. The response of the tumor was similar in both group I and group II. p53 protein was not expressed in the normal esophageal mucosa. A high level of p53 in operated specimens was associated with unfavorable tumor response to preoperative treatment. Therefore, immunohistochemical detection of p53 protein can be considered to predict the outcome of preoperative therapy.
Dis Esophagus 1999
PMID:p53 Protein accumulation as a prognostic marker of preoperative radiotherapy and/or chemotherapy in advanced squamous cell esophageal carcinoma--preliminary report. 1046 45


1 2 3 4 5 6 7 8 9 Next >>