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)

Despite the steadily increasing number of patients suffering from squamous-cell carcinomas of the oropharyngeal region, little is known about the molecular steps involved in the induction of these neoplasms. We investigated oropharyngeal cancers from 38 patients for mutations in the p53 tumour-suppressor gene. The majority of patients (74%) had a history of tobacco and alcohol abuse. Five had lymph-node metastases, 3 had multiple primary carcinomas and 2 presented with multiple primary tumours and lymph-node metastases. Exons 5 through 8 of the p53 gene were screened by single-strand conformation polymorphism analysis followed by direct DNA sequencing. A total of 16 tumours (42%) contained point mutations which were scattered throughout exons 5 to 8. Most mutations (56%) were transitions, predominantly G-->A. Among the transversions, G-->T mutations prevailed; these have also been found in smoking-related lung cancer. One carcinoma of the soft palate showed a mutation which was retained in a lymph-node metastasis. In another patient, 2 primary carcinomas had different mutations, indicating that they had developed independently. Similar results were obtained in a case with a p53 mutation in the third of 3 primary tongue carcinomas which developed over a period of 23 years. One lymph-node metastasis had a 12-bp deletion which was not detected in any of the primary malignancies. The frequent occurrence of p53 mutations in oropharyngeal carcinomas supports the view that they play a role in the initiation or progression of the malignant phenotype.
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PMID:p53 gene mutations in oropharyngeal carcinomas: a comparison of solitary and multiple primary tumours and lymph-node metastases. 811 70

Six synchronous gastrointestinal primaries were identified in a 70 year old male with no known cancer predisposition syndrome or recognized risk factors except alcohol abuse. These specimens appeared to be independent and unrelated by gross and histopathological examination. In order to further evaluate the six tumors, we analyzed selected DNA sequences for alterations in the K-ras oncogene and p53 tumor suppressor gene. In addition, three loci were analyzed to determine microsatellite instability. Using the polymerase chain reaction, single stranded conformational polymorphism, and DNA sequencing, we demonstrated that each primary manifests genetic characteristics typical of the tissue of origin. In addition, one primary, a moderately differentiated colon adenocarcinoma, exhibited mutations not detected in the other specimens. This study suggests that these synchronous primaries arose independently and progressed along different carcinogenic pathways.
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PMID:Multiple synchronous primaries of the gastrointestinal tract: a molecular case report. 901 74

Oral cancer has increased recently in Australia, and overall survival rates have not improved in the past 30 years. Dentists are uniquely well placed to screen their patients at regular recall examinations and detect cancers or pre-cancerous lesions at an early curable stage. Although the major risk factors--tobacco smoking and alcohol abuse--have been identified, only a minority of patients at-risk will develop oral cancer. Molecular analysis has now detected an accumulation of genetic lesions in oral cancer, but the earliest molecular changes in the oral epithelium in the progression to malignancy in at-risk patients has not yet been determined. These changes could if known be exploited for screening purposes. How long human oral carcinogenesis takes to progress from the initiated cell to an invasive tumour, and whether molecular biology can be used to identify the minority of patients who will develop cancer from the large population exposed to the risk factors, are other important unanswered questions. p53 tumour suppressor gene mutations are the most frequently found genetic errors in oral cancer and the p53 gene is a likely target for tobacco and alcohol.
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PMID:A general review of the p53 gene and oral squamous cell carcinoma. 1089 14

Tongue cancer involving the anterior tongue often presents at an early stage. The aetiology is strongly associated with smoking and alcohol abuse similar to other squamous cell carcinomas (SCC) of the head and neck (HN). Surgery and radiotherapy, either alone or together, offer the prospect of cure in the majority of patients. However, there remains a group of younger patients less than 40 years old for whom outcome is often poor. Presented here is the case of a 24-year-old woman who developed SCC of the anterior tongue. Despite treatment, loco-regional relapse occurred resulting in death. The literature identifies a distinct subgroup of younger patients who develop HN SCC, particularly of the oral cavity. The aetiology remains unclear. Recent studies have looked at the prognostic significance of various new non-clinico-pathological markers in HN SCC (including p53 tumour suppressor gene, cyclin D1 protein, Ki 67 antigen and tumour angiogenesis). The majority of these studies, as expected, have involved the typical HN patient (male, aged > 60 years old). However, the relevance of these studies is of likely importance to all patients diagnosed with HN SCC. The recent use of these non-clinical-pathological markers in HN SCC, including reference to such studies in younger patients, is discussed. The English literature during the past 30 years is reviewed with reference to the diagnosis of tongue SCC in younger patients.
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PMID:Tongue cancer in younger patients. 1090 75

Pancreatic cancer belongs to the neoplasms which are characterised by increasing morbidity and mortality. Five-year survival rates of about 0.4% are the norm, and little has changed in the last 70 years. Important etiological factors are age, sex, diet, tobacco smoking, alcohol abuse, occupation and chemical exposure, hereditary chronic pancreatitis, and previous surgery (cholecystectomy and gastrectomy). The majority of exocrine tumours of the pancreas are malignant and 80-90% of them comprise ductal adenocarcinomas. The development and growth of pancreatic carcinoma appears to be caused by a progressive accumulation of multiple genetic abnormalities. This includes oncogene (K-ras) activation, loss of tumour-suppressor p53 gene function and overexpression of growth factors and their ligands. The morphological background for the development of pancreatic carcinoma is ductal epithelial hyperplasia. Current molecular studies have resulted in the identification of cell clones exhibiting the same genetic alterations (K-ras and p53 mutations) as in infiltrating pancreatic carcinoma. Pancreatic intraepithelial neoplasia is only partially defined. The purpose of our study was to evaluate Ki-67 proliferative index and HER-2/neu gene expression in pancreatic intraepithelial proliferative lesions as a sign of increasing epithelial proliferation and dysplasia. Additionally we made an attempt to apply morphometry in demarcating between intraepithelial proliferations of "reactive" type and proliferations with tendency towards progression to cancer. Another aim of the study was to evaluate the expression of bcl-2 and p53 genes in various types of pancreatic intraepithelial proliferations and in pancreatic cancer and to answer the question whether they interact in the process of pancreatic intraepithelial neoplasia. We have also undertaken investigations aiming at determination of the CD44s gene and its v6 isoform expression in intraductal and invasive pancreatic carcinoma, attempting to correlate this expression with the p53 gene mutations. The results of our study indicate that intraductal pancreatic proliferations form a group of heterogeneous lesions possessing different proliferative activity of cells, karyometric features and HER-2/neu, bcl-2 and p53 genes expression. The precancerous lesion in the pancreas may be atypical papillary hyperplasia, which is similar to intraductal carcinoma with respect to the proliferative activity of cells and HER-2/neu, bcl-2 and p53 expression. Pancreatic carcinoma is characterised by high p53, CD44s and CD44v6 expression and low bcl-2 expression. CD44 and p53 genes expression is independent and between bcl-2 and p53 expression there is an inverse correlation. The p53 and CD44v6 expression is the higher the lower is the histological grade of the pancreatic carcinoma.
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PMID:[Morphologic, morphometric and immunohistochemical studies on pancreatic intraductal hyperplasia and infiltrating carcinoma]. 1090 69

Hepatocellular carcinoma (HCC) is a major type of primary liver cancer and one of the rare human neoplasms etiologically linked to viral factors. Chronic infections with the hepatitis B virus (HBV) and the hepatitis C virus (HCV) have been implicated in about 80% of cases worldwide, and other known environmental risk factors, including alcohol abuse and dietary intake of aflatoxin B1, might synergize with viral infections. Recent insight into the molecular mechanisms leading to HCC development has been provided by the identification of major genetic abnormalities revealed by genomewide allelotype studies and molecular cytogenetic analysis. Moreover, several oncogenic pathways have been implicated in malignant transformation of liver cells. Inactivation of the p53 tumor suppressor gene by mutations and allelic deletions in about 30% of HCC cases has been associated predominantly with exposure to aflatoxin B1 and HBV infection. By contrast, a mutation in the beta-catenin gene in around 22% of HCCs is more rare in HBV-associated tumors. Activation of cyclin D1 and disruption of the Rb pathway are also commonly involved in liver tumorigenesis. New major challenges include the identification of candidate genes located in frequently altered chromosomal regions and that of oncogenic pathways driven by different risk factors. This search might shed some light on the tumorigenic role of HBV and HCV. It might also permit accurate evaluation of major targets for prognostic and therapeutic intervention.
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PMID:Genetic alterations and oncogenic pathways in hepatocellular carcinoma. 1209 25

The aim of our study was to examine the case histories of patients with intraductal papillary mucinous tumor (IPMT) treated with resection to determine predictors of prognosis. Between 1989 and 2000, all patients treated with pancreatic resection for IPMT (n = 63) were analyzed. The diagnosis of IPMT was made using the surgical specimen and the World Health Organization definition. Predictors were determined using univariate and multivariate analysis. The pathologic findings were benign (n = 30), carcinoma in situ (CIS; n = 5), and invasive carcinoma (n = 28). After univariate analysis, predictors of malignancy (invasive plus CIS) were jaundice (odds ratio = 10.32), elevated serum CA19-9 (odds ratio = 15.0), any abnormal liver function test (odds ratio = 7.69), and p53 overexpression. The only predictor of benign disease was gross mucus observed during endoscopy (odds ratio = 4.35). After multivariate analysis, predictors of malignancy were any abnormal liver function test (odds ratio = 5.09) and p53 overexpression, whereas the only predictor of benign disease was still gross mucus (odds ratio = 5.88). Actuarial 3- and 5-year survival for benign disease was 95% and 83% and for malignant disease 52% and 44%, respectively (P = 0.0048). Survival curves also favored p53-negative tumors vs. p53-positive tumors (P = 0.0055). In the 33 patients with malignant disease (mean follow-up time = 35 months), the presence of gross mucus was a predictor of prolonged survival after univariate and multivariate analysis (odds ratio = 4.34 and 4.55, respectively), whereas alcohol abuse was a predictor of poor survival (odds ratio = 3.41 and 3.60, respectively). Gross mucus observed during endoscopy is a predictor of benign IPMT and, within the group with malignant IPMT; the presence of gross mucus was associated with better survival. Survival was also strongly associated with either benign IPMT or negative staining for p53 overexpression.
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PMID:Mucus is a predictor of better prognosis and survival in patients with intraductal papillary mucinous tumor of the pancreas. 1255 80

Head and neck squamous cell carcinoma is a disease associated with tobacco and alcohol abuse. There is evidence that the oncogenic human papillomavirus (HPV) may also be a risk for upper aerodigestive tract cancers. High-risk HPVs encode two early proteins, E6 and E7, that can bind to p53 and pRb, respectively, and induce its degradation or inactivation. The TP53 gene has a single polymorphism at codon 72 of exon 4 that encodes either arginine (Arg) or proline (Pro). The purpose of this study was to evaluate the role of HPV infection and TP53 polymorphism in head and neck cancer. We analyzed 50 tumors, as well swabs of oral mucosa from 142 control individuals, with a polymerase chain reaction technique. The prevalence of HPV in controls was 10.6% and in cancer specimens 16%. The frequency distribution of genotypes in controls was 50% Arg/Arg, 43% Arg/Pro and 7% Pro/Pro; in tumors, it was 52% Arg/Arg, 32% Arg/Pro, and 16% Pro/Pro. Contrary to the results of some studies on cervical cancer, no association between any TP53 genotype or allele and the development of head and neck cancer was observed, regardless of HPV status, except for the Pro/Pro genotype, which is associated with the absence of HPV. The arginine allele appears to protect against head and neck cancers. Also, the data showed that HPV infection results in no increased risk of developing head and neck tumors.
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PMID:Analysis of human papillomavirus prevalence and TP53 polymorphism in head and neck squamous cell carcinomas. 1504 Dec 22

Hepatocellular carcinoma (HCC) is the most common primary tumor of the liver worldwide. The incidence of HCC is increasing in North America secondary to rises in chronic liver disease from alcohol abuse and viral hepatitis. HCC most commonly metastasizes hematogenously or through lymphatics to the lungs and regional lymph nodes. Involvement of small bowel is rare and typically results from direct invasion and extension. We examined the molecular features related to this extremely rare case of isolated duodenal metastasis of HCC and noted p53 and Ki-67 positive staining. Here, we review the possible molecular and immunohistochemical studies that may aid definitive diagnosis and the evidence for the management of metastatic hepatocellular carcinoma.
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PMID:A rare case of isolated duodenal metastases from hepatocellular carcinoma associated with p53 and ki-67 expression: a case report. 2006 99

Alcohol dependence is a major disease burden of adults in modern society worldwide. There is no cure for alcohol dependence. In this study, we have examined the molecular targets of ethanol-induced toxicity in humans based on a systematic review of literature data and then discussed current and potential therapeutic targets for alcohol abuse and dependence. Using human samples with ethanol exposure, microarray analyses of gene expression have shown that numerous genes are up- and/or down-regulated by alcohol exposure. The ethanol-responsive genes mainly encode functional proteins such as proteins involved in nucleic acid binding, transcription factors, selected regulatory molecules, and receptors. These genes are also correlated with important biological pathways, such as angiogenesis, integrin signalling pathway, inflammation, wnt signaling pathway, platelet-derived growth factor signaling pathway, p53 pathway, epidermal growth factor receptor signaling pathway and apoptosis signaling pathway. Currently, only three medications were approved by the U.S. Food and Drug Administration (FDA) for the treatment of alcohol abuse and alcohol dependence, including the aldehyde dehydrogenase inhibitor disulfiram, the micro-opioid receptor antagonist naltrexone, and the N-methyl-D-aspartate (NMDA) receptor inhibitor acamprosate (oral and injectable extended-release formulations). In addition, a number of agents are being investigated as novel treatments for alcohol abuse and dependence. These include selective 5-HT reuptake inhibitors (e.g. fluoxetine), 5-HT(1) receptor agonists (e.g. buspirone), 5-HT(2) receptor antagonists (e.g. ritanserin), 5-HT(3) receptor antagonists (e.g. ondansetron), dopamine receptor antagonists (e.g. aripiprazole and quetiapine), dopamine receptor agonists (e.g. bromocriptine), GABA(B) receptor agonists (e.g. baclofen), and cannabinoid-1 (CB(1)) receptor antagonists. Some of these agents have shown promising efficacy in initial clinical studies. However, further randomized studies with larger samples are warranted to establish their efficacy and safety profiles in the treatment of alcohol dependence.
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PMID:Identification of molecular targets associated with ethanol toxicity and implications in drug development. 2018 50


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