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)

Genetic alteration of the p53 gene was examined in tissue specimens of primary gallbladder cancer (GBC) using PCR-single strand conformation polymorphism (SSCP) and direct sequencing analyses. The p53 gene mutation was detected in five of the 16 GBC cases examined (31%). All five cases showed single point mutations; four were mutations resulting in amino acid substitution and the other was one base-pair deletion. Of the five mutations detected, four occurred at evolutionarily conserved regions and the remaining one at a well conserved region among species. Our result is similar to those of previous reports for various human cancers in mutation scattering over four of the five conserved domains.
 ...
PMID:Mutation of the p53 gene in gallbladder cancer. 807 40

In gallbladder carcinoma, studies on the prime target of genetic alterations and gene therapy in human gallbladder malignancies, the p53 tumor suppressor gene, have been focusing on this gene's immunohistochemical detection. From November 1991 to October 1993, seven patients suffering from gallbladder carcinoma underwent surgical resection. Cancerous and normal liver tissues were obtained immediately after surgery, snap-frozen in liquid nitrogen, and stored at -80 degrees C for immunohistochemistry and DNA isolation. Exons 5, 6, 7, and 8 of the p53 gene were completely sequenced following polymerase chain reaction (PCR) amplification of a 1574-bp fragment. Missense mutations were detected in the cancerous tissues of two patients: one transition each on codons 134 (Phe-->Leu) and 146 (Trp-->Arg). Immunohistochemical p53 staining was positive in the latter patient only. This is the first report on sequence analysis and mutagenesis of the p53 gene in Caucasian patients with gallbladder cancer. Both mutations were transitions and seem to represent a rather rare event. The possible impact of p53 mutagenesis on gallbladder tumorigenesis requires evaluation in larger studies.
 ...
PMID:p53 hot-spot mutational analysis in advanced Western gallbladder carcinoma. 927 9

It is well known that the frequency of an associated gallbladder cancer in patients with pancreaticobiliary maljunction (PBM) without congenital choledochal dilation (CCD) is very high, while that of bile duct cancer with CCD is remarkably high, and that of bile duct malignancy without CCD is low. However, recent statistical evaluations have demonstrated that the coincidence rates of gallbladder and bile duct cancer with CCD are 11.5% and 4.6%, respectively, whereas without CCD the rates are 57.1% and 4.1%, respectively. Rates of bile duct cancer with CCD are comparable to those without CCD. We have performed biliary reconstruction after resection of extrahepatic bile ducts along with the gallbladder for PBM patients who had neither CCD nor cancer. Our surgical strategy for these patients without CCD with PBM was assessed from K-ras point mutations and overexpression of p53 protein in the epithelia of the cancerous portions and non-neoplastic portions of the gallbladder and bile duct affected by PBM regardless of choledochal dilatation. The mutation rate in the non-neoplastic gallbladder epithelium without CCD was 80%, that of the bile duct without CCD 57%, not significantly different from the 50% and 40%, respectively, with CCD. The frequency of p53 overexpression in the non-neoplastic bile duct epithelium without CCD was 14%, comparable to the 11% in gallbladder epithelium with CCD. Judging from the statistical data and the molecular biological data, resection of an extrahepatic bile duct with the gallbladder should be the treatment of choice for carcinogenesis prevention.
 ...
PMID:Surgical strategy for patients with pancreaticobiliary maljunction without choledocal dilatation. 944 27

To diagnose early gallbladder carcinoma is difficult but essential to improve the survival of the patients with this cancer. Fifty-three early gallbladder cancers were macroscopically divided into protruding and flat types. The diagnostic devises [ultrasonography (US), computed tomography (CT), and drip infusion cholangiography (DIC)] were compared for their ability of early detection. The specimens were examined cytologically for diagnosis during operation and the p53 protein was investigated. Thirty-three cases were of the protruding type, eighteen of the flat type, and two unclassified. Carcinoma tended to be missed when gallstones were present. Preoperative diagnosis of the flat type was difficult. Tumor location did not always correlate with the preoperative diagnosis. Of the misdiagnosed cases of the protruding type, half were missed with US and CT and were not visualized clearly by DIC. Among the flat type cancers, only three had no abnormal findings by diagnostic imaging. Cytologic examination was effective, and p53 was expressed only in early carcinoma, not in adenoma or dysplasia. Even in the presence of gallstones or cholecystitis, any abnormal findings should make one suspicious of gallbladder cancer. Cytology and p53 expression may be useful for the intraoperative diagnosis, and a combination of diagnostic methods is important.
 ...
PMID:Diagnostic imaging of early gallbladder cancer: retrospective study of 53 cases. 1039 May 91

Carcinoma of the gallbladder has an unusual geographic and demographic distribution being more common in Israel, Bolivia, Chile and in Southwestern native Americans in the United States. Chronic cholecystitis, choledochal cysts and significantly high body mass index are associated risk factors. Over 90% of gallbladder carcinomas are adenocarcinomas. Advanced local and regional disease usually is present at the time of diagnosis. P53 protein overexpression and p53 mutation may be related to increasing grade of cytologic atypia and to invasiveness. K-ras gene mutation occurs in both dysplasia and carcinomas. Ultrasonography, CT, MRI are diagnostic measures that can provide accurate staging information. Overall, the curative resection rates for gallbladder carcinoma range from 10% to 30%. During laparoscopic cholecystectomy, gallbladder cancer may be inadvertently discovered necessitating a more extensive resection. For those with unresectable disease, palliative surgical, endoscopic or radiologic bypass procedures can improve quality of life. Other approaches to the management of advanced tumors include combined radiation and chemotherapy and systemic chemotherapy.
 ...
PMID:Gallbladder carcinoma. 1043 4

Hepatobiliary neoplasms comprise a significant portion of the worldwide cancer burden. Advances in basic science research have led to rapid progress in our understanding of the molecular events responsible for these dreaded diseases. The genetic changes associated with hepatocellular carcinoma (HCC) have received the most attention. Aflatoxin B1 exposure leads to mutations in the p53 tumor suppressor gene, most commonly a transversion in codon 249 that leads to a substitution of serine for arginine in the p53 protein. Numerous other tumor suppressor genes, oncogenes, and tumor gene pathways are altered in HCC. Hepatitis B virus (HBV) infection is strongly associated with HCC. HBV may cause HCC either directly via the HBV X protein, or indirectly by causing liver inflammation and cirrhosis. Hepatitis C virus (HCV) infection is also associated with HCC. Recent evidence suggests that the HCV core protein may play a role in hepatocarcinogenesis. Several inherited metabolic diseases are associated with HCC. It is likely that these diseases cause HCC indirectly by causing cirrhosis. The molecular pathogenesis of cholangiocarcinoma and gallbladder cancer has not been well defined. However, multiple tumor suppressor genes and oncogenes, including p53 and K-ras, are altered in these tumors. Further molecular characterization of hepatobiliary tumors may lead to earlier diagnosis, better staging, improved treatment planning, and the development of more effective therapies.
 ...
PMID:Genes and viruses in hepatobiliary neoplasia. 1112 84

Malignant diseases of the digestive tract cause more than 50% of deaths due to cancer in Chile. There is a high incidence of gastric and gallbladder cancer and an increasing frequency of colorectal cancer. P53 tumor suppressor gene has a great importance in carcinogenesis and its alterations are specially important in digestive tract tumors such as colorectal cancer. There is contradictory evidence about the frequency of p53 gene or protein alterations or their biological significance. There is little information about p53 in Chile and it is mostly limited to immunohistochemical studies. This revision analyzes the frequency of p53 alterations in digestive tract tumors in Chile, using immunohistochemical and molecular biology methods. A special emphasis is given to the prognostic importance of this gene.
 ...
PMID:[P53 tumor suppressor gene in digestive neoplasms]. 1134 16

The purpose of this review is to evaluate our current knowledge of the embryologic etiology of pancreaticobiliary maljunction (PBM), its diagnosis, clinical aspects, and treatment, and to clarify the mechanisms of PBM involvement in carcinogenesis. Although the embryologic etiology of PBM still awaits clarification, an arrest of the migration of the common duct of the biliary and pancreatic ducts inwards in the duodenal wall has hitherto been speculated to result in a long common channel in PBM. However, we propose the hypothesis that the etiology of PBM is caused by a disturbance in the embryonic connections (misarrangement) of the choledochopancreatic duct system in the extremely early embryo. That is, PBM is an anomaly caused by a misarrangement whereby the terminal bile duct joins with a branch of the ventral pancreatic duct system, including the main pancreatic duct. PBM is frequently associated with congenital bile duct cyst (CCBD). However, these two anomalies are thought to have different embryonic etiologies. The diagnostic criteria for PBM are the radiological and anatomical detection of the extramural location of the junction of the pancreatic and biliary ducts in the duodenal wall. However, in PBM patients with a short common duct (less than 1 cm in length), detection of the extramural location is difficult. The clinical features of PBM are intermittent abdominal pain, with or without elevation of pancreatic enzyme levels; and obstructive jaundice, with or without acute pancreatitis, while the clinical features of PBM patients with CCBD are primary bile duct stone and acute cholangitis. The optimum approach for the treatment of PBM is the prevention of the reciprocal reflux of bile and pancreatic juice in the pancreas and the bile duct system. To achieve these aims, the surgical approach is most effective, and complete biliary diversion procedures with bile duct resection (for example, choledochoduodenostomy or choledochojejunostomy of the Roux-en-Y type) are most useful. Recently, it has been recognized that the development of biliary ductal carcinoma is associated with PBM. That is, the development of gallbladder cancer occurs frequently in PBM patients without CCBD, and bile duct cancer originating from the cyst wall also occurs in PBM patients with CCBD. It is speculated that the pathogenesis of the bile duct or gallbladder cancer in PBM patients involves the reciprocal reflux of bile and pancreatic juice. Investigations of epithelial cell proliferation in the gallbladder of PBM patients, and of K- ras mutations and p53 suppressor gene mutations, loss of heterozygosity of p53, and overexpression of the p53 gene product in gallbladder cancer and noncancerous lesions in PBM patients have been carried out in various laboratories around the world. The results support the conclusion that PBM is a high risk factor for the development of bile duct carcinoma.
 ...
PMID:Recent advances in pancreaticobiliary maljunction. 1202 97

Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive lipid-storage disorder characterised by xanthomas, neurological dysfunctions and premature atherosclerosis. A case of a well differentiated adenocarcinoma of the gallbladder occurring in a 57-year-old Japanese man with CTX, confirmed clinically, biochemically and at autopsy is reported together with analyses of the sterol 27-hydroxylase (CYP27) and p53 genes. A missense mutation of the p53 (G for C) was detected in the gallbladder adenocarcinoma. Direct sequence analysis also showed a silent mutational substitution of unknown significance, C for A, in CYP27 at codon 89. In the past, CTX patients have only demonstrated this infrequently, indicating no direct relationship between CYP27 dysfunction and tumour development. Thus, the present case of gallbladder cancer appears to be a chance occurrence.
 ...
PMID:An autopsy case of gallbladder cancer developing in a Japanese man with cerebrotendinous xanthomatosis: genetic analysis of the sterol 27-hydroxylase and p53 genes. 1274 62

Our goal has been to investigate the expression and correlated significance of inducible nitric oxide synthase (iNOS) and P53, Bax in benign and malignant gallbladder diseases. We detected the expression of iNOS, P53 and Bax in the gallbladder wall by SP immunohistochemistry in 16 cases of chronic cholecystitis, 11 cases of chronic cholecystitis with adenomyoma and 24 cases of gallbladder adenocarcinoma. The percentage of positively marked tumor cells was counted under microscope and the intensity of immunoreactivity was graded. SPSS10.0 statistical software was applied for statistical analysis. In this study, we found that: (1) Both benign and malignant diseased gallbladder wall expressed iNOS and Bax. Compared to benign diseased gallbladders, their expression in adenocarcinoma was decreased (p < 0.05), P53 was expressed strongly only in nuclei of adenocarcinoma cells of some cases. (2) In benign and malignant diseased gallbladders, iNOS expression was related positively to Bax (p < 0.01), the expression of P53 and Bax had a negative relationship (p < 0.01). The results suggested that both chronic cholecystitis and chronic cholecystitis with adenomyoma carry the risk of becoming malignant, especially the latter. NO is an important mediated molecule in cancer, there are intimate relationships between gallbladder cancer and apoptosis.
 ...
PMID:Correlated expression of inducible nitric oxide synthase and P53, Bax in benign and malignant diseased gallbladder. 1470


1 2 3 4 5 Next >>