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)

Disruption of cell cycle controls is a pathognomonic feature of all malignant cells. Therefore, we immunohistochemically investigated the relationship between cell cycle regulatory proteins and clinicopathologic features in order to identify the biomarkers related to the outcome of patients with biliary tract cancer (BTC). A cohort of paraffin-embedded specimens were selected from 36 patients, including 18 gallbladder and 18 extrahepatic bile duct cancers, who underwent curative or palliative surgical resection at Korea University Medical Center from June 1998 to December 2004. Tissue microarrays were used to investigate the immunohistochemical staining for p21, p27, p53, cyclin D1, bcl2, and Ki-67. Univariate and multivariate survival analyses were performed to determine the prognostic significance of each protein expression. Absence of p21 expression independently predicted poor outcome in all cases. Well-differentiated tumor was found to be an independent good prognostic factor in gallbladder cancer. Absence of p21 expression and moderately to poorly differentiated tumor were found to be an independent poor prognostic factor in patients with negative for neural invasion. Absence of p21 and bcl2 were found to be an independent poor prognostic factor in patients with no lymph node metastasis. Absence of p21 expression was a significant independent poor prognostic factor in BTC, partly in patients with biologically less aggressive phenotypes. This finding suggests that determination of p21 expression in surgically resected specimens may provide prognostic information in addition to conventional pathologic findings for patients with BTC, especially those who have biologically less aggressive phenotypes.
 ...
PMID:Expression and clinical significance of cell cycle regulatory proteins in gallbladder and extrahepatic bile duct cancer. 1897 38

Pancreaticobiliary maljunction (PBM) is associated with the occurrence of biliary cancer due to pancreatobiliary reflux. We present a case of simultaneous double cancer of the gallbladder and bile duct. A 77-year-old woman who had jaundice, intra- and extra-hepatic biliary ductal dilatation and a space-occupying lesion in the gallbladder and lower bile duct underwent pancreatoduodenectomy. The gallbladder cancer showed papillary carcinoma without mutation of the K-ras gene and with p53 non-sense mutation of CCA (Pro) to CA (Stop) on codon 301 in exon 8. The bile duct cancer revealed a well-differentiated adenocarcinoma without mutation of the K-ras gene and with p53 miss-sense mutation of GTG (Val) to GAG (Glu) on codon 272 in exon 8. There were no mutations of either the K-ras or p53 gene in non-cancerous epithelia. In contrast, only the mucosa of the common channel had p53 protein accumulation and high cell proliferation activity. Therefore, the genetic pathway might be the same in both the gallbladder and bile duct cancer, and a high potential for carcinogenesis might be present in the epithelium of the common channel in patients with PBM.
 ...
PMID:p53 gene mutation and p53 protein overexpression in a patient with simultaneous double cancer of the gallbladder and bile duct associated with pancreaticobiliary maljunction. 1918 32

Mitosis dysregulation is common in cancers. This study explored the nuclear expression patterns and prognostic significance of mitotic regulatory proteins, including Aurora kinases, survivin, and p53, in biliary tract cancer (BTC). Archival tumor samples from 161 BTC patients who underwent surgery were tested for the expression of Aurora-A, Aurora-B, survivin, and p53 by immunohistochemistry. The potential endogeneity among the clinicopathologic variables and survival outcome was assessed by a generalized simultaneous equations model. Nuclear overexpression of Aurora-A, Aurora-B, survivin, and p53 was found in 79 (49.1%), 45 (28.0%), 55 (34.2%), and 55 (34.2%) patients, respectively. Intrahepatic cholangiocarcinoma, compared with the other two subtypes, had significantly higher proportions of nuclear overexpression of Aurora-B and survivin (37.8% and 47.3%, respectively). Simultaneous overexpression of Aurora-A and Aurora-B was correlated with that of p53. Overexpression of Aurora-B was also correlated with that of survivin and tumor grade. Our data indicate that simultaneous overexpression of Aurora-A and Aurora-B, suggesting dysregulated mitosis is associated with worse survival in patients with BTC. Independent prognostic factors for poor overall survival included simultaneous overexpression of Aurora-A and Aurora-B (hazard ratio, 1.997; 95% confidence interval, 1.239-3.219; P = 0.0045) and tumor grade (hazard ratio, 2.117; 95% confidence interval, 1.339-3.348; P = 0.0013) assessed by a multivariate analysis stratified by American Joint Committee on Cancer stage and p53 overexpression. Endogeneity testing suggested that nuclear overexpression of p53 and tumor type may influence patient survival through their interactions with Aurora-A/Aurora-B expression and tumor grade.
 ...
PMID:Nuclear overexpression of mitotic regulatory proteins in biliary tract cancer: correlation with clinicopathologic features and patient survival. 1919 Jan 45

With the help of my colleagues, I have been conducting epidemiological studies on biliary tract cancer (BTC), including gallbladder cancer (GBC) and extrahepatic bile duct cancer (BDC), in Japan and Chile for about 19 years. Clustered areas with high mortality rates, especially for female GBC were found to correspond with places or prefectures in Japan that were famous for rice production. The roles of known risk factors, such as gallstones and cholecystitis, were examined, but no single factor was implicated in the high mortality rates for GBC in these areas. A working hypothesis, called the "rice production hypothesis" was formulated; this initial hypothesis was replaced by a new multifactorial causation hypothesis: GBC is more likely to occur in individuals with a genetic susceptibility and a past history of gallstones or cholecystitis who are exposed to geographically specific environmental factors, such as agricultural chemicals. On the basis of various analytical studies, it is concluded that a certain agricultural chemical was responsible for the occurrence of GBC. At the time of writing, no evidence has been obtained to disprove our hypothesis. We have also conducted international collaborative studies in Chile, which has the highest mortality rate for GBC in the world. Bile from Chileans was found to have a higher mutagenic activity than that from Japanese subjects; Chileans with a history of constipation or a habit of consuming red chilli pepper had a high risk of developing GBC, if they also had gallstone(s). The presence of a regional difference in p53 mutagenesis was also observed.
 ...
PMID:Epidemiological studies on the distribution and determinants of biliary tract cancer. 2143 89

The prognosis of biliary tract cancer is still poor. Although a number of clinical studies have suggested a role for radiation therapy in advanced biliary tract cancer, its value remains controversial. Moreover, the intrinsic radiosensitivity of bile duct cancer cell lines has not been described, and the molecular basis for the response of these tumors to ionizing radiation is poorly understood. The present study was designed to examine the intrinsic radiation sensitivity of human biliary tract cancer cells and its relationship to p53 status. Radiation response expressed by the parameters n, D-0, D-10, alpha, beta, (D) over bar (mean inactivation dose), and SF, of seven cell lines derived from gallbladder and bile duct cancers was determined. The results suggest that biliary tract cancer cell lines as a group are relatively radioresistant. The mean X-ray survival parameters for these seven cancer cell lines were D-0=2.13+/-0.29 Gy, D-10=5.73+/-0.59 Gy, (D) over bar=2.76+/-0.25 Gy, alpha=0.25+/-0.03, and SF2=0.54+/-0.05. One of the seven lines was more radiosensitive than the others (D-0=0.77+/-0.02 Gy, D-10=2.95+/-0.06 Gy, (D) over bar=1.57 Gy, alpha=0.35, SF2=0.35+/-0.03). Five of six lines examined expressed mutant p53 including the radiosensitive line; one radioresistant line expressed wild-type p53. Thus, although loss of wild-type p53 expression occurred frequently in these biliary cancer cell lines, radiosensitivity did not correlate with p53 status. In view of the intrinsic radioresistance of this type of tumor cell coupled with the poor tolerance of surrounding normal tissues, maximal surgical debulking and intraoperative radiation therapy may contribute to increased local control over resection and/or conventional fractionated radiotherapy.
 ...
PMID:Radiosensitivity of human biliary tract cancer cell lines in vitro. 2153 11

Background. Recent diagnostic imaging tests contribute to improving the diagnosis of pancreatobiliary cancers. However, it is not practical to perform these tests for all patients as screening. Thus, less-invasive and simple screening tests are still required. A method to detect the IgG antibody induced in serum against the p53 protein accumulating due to p53 gene mutation, as a biomarker, was developed around 1990. Method. 35 patients with pancreatic cancer, 12 patients with biliary tract cancer, and 31 patients with benign pancreatobiliary diseases were entered into this study. Measurement of serum anti-p53 antibody was conducted in all patients. In addition, the rate of p53 protein overexpression was examined in those cases that could be examined pathologically. Result. Among all patients in the pancreatic cancer and biliary tract cancer groups, there was no patient with serum anti-p53 antibody positive value that exceeded the standard value. The rate of p53 protein overexpression was 48.0% in the patients with pancreatobiliary cancers and 0% in the benign pancreatobiliary diseases group. Conclusion. Serum anti-p53 antibody measurement does not contribute to the diagnosis of pancreatobiliary cancers. Instead, traditional p53 immunostaining still appears to be valuable in combination with standard procedures.
...
PMID:Serum p53 Antibody Is Not Associated with p53 Immunoreactivity in Patients with Pancreatobiliary Cancers. 2445 72

Biliary tract cancers have an extremely poor outcome, and specific diagnostic markers and effective treatments are needed urgently. In this study, we assessed the capacity of panel of immunohistochemical markers including claudin-18, maspin, and p53 to distinguish biliary tract carcinoma and biliary intraepithelial neoplasia (BilIN) from non-neoplastic epithelium. We performed a retrospective study of 66 biliary tract cancer specimens and 63 specimens with non-neoplastic lesions. Of the surgical specimens, 96.7 % with adenocarcinoma/BilIN were detected as neoplastic, and all 63 specimens histologically diagnosed as non-neoplastic lesion were detected as non-neoplastic with high sensitivity (91.1 %) and specificity (100 %). Of presurgical endobiliary forceps biopsy specimens, all with adenocarcinoma/BilIN and only 1 of the 19 with a non-neoplastic lesion were distinguished as neoplastic with high sensitivity (100 %) and specificity (94.7 %). Moreover, this panel provided good separation of neoplasm from malignancy-undetermined atypical epithelium (18/21, 85.7 %). This panel achieves a more reliable distinction of biliary tract cancers and BilINs from non-neoplastic epithelia in both surgical and biopsy specimens than immunohistochemical analysis with single antibodies and is useful in supporting a diagnosis of adenocarcinoma and BilIN.
 ...
PMID:An immunohistochemical marker panel including claudin-18, maspin, and p53 improves diagnostic accuracy of bile duct neoplasms in surgical and presurgical biopsy specimens. 2550 75

A 58-year-old man was diagnosed with liver dysfunction during a health exam and subsequently visited a doctor. Abdominal ultrasonography revealed space-occupying lesions in the gall bladder and bile duct, and he was hospitalized for further examination and treatment. Computed tomography (CT), endoscopic retrograde cholangiopancreatography (ERCP), and magnetic resonance cholangiopancreatography (MRCP) revealed double cancer of the gall bladder and bile duct with pancreaticobiliary maljunction (PBM), and we performed a pancreatoduodenectomy. Pathological examination revealed gall bladder and bile duct cancer, and severe dysplasia of the papilla of Vater. We diagnosed synchronous triple cancer because none of the cancers had continuity or vascular invasion. Each cancer was at Stage I, and the patient has survived for 2 years and 6 months without recurrence and no additional treatment. PBM is a mutation of the junction of the pancreatic and bile ducts outside of the duodenal wall, and is a known complication of biliary tract cancer due to the reflux of pancreatic juice and bile. Because K-ras and p53 gene mutations occur in the biliary tract mucosal epithelium, PBM increases the risk of developing multicentric cancer. It is important to consider the existence of double cancer when biliary tract cancer is detected in a PBM patient.
 ...
PMID:[A case of synchronous cancer of the gall bladder, common bile duct, and the papilla of vater]. 2573 Dec 39

Gallbladder cancer (GBC) is the most common and aggressive type of biliary tract cancer. There are various histological types of GBC, and the vast majority of GBC cases are adenocarcinomas. Squamous and adenosquamous carcinomas are rare GBC subtypes that are traditionally considered to be more aggressive and to be associated with a poorer prognosis than adenocarcinoma. Galectin-9 (Gal-9), a tandem-repeat-type galectin, has been reported to induce apoptosis-mediated elimination of various cancers, including hepatocellular carcinoma, cholangiocarcinoma, and hematologic malignancies. Therefore, we investigated the antitumor effects of Gal-9 on GBC in vitro and in vivo. In our in vitro experiments, Gal-9 suppressed cell proliferation in various GBC cell lines but not in the OCUG-1 cell line, which represents a poorly differentiated type of adenosquamous carcinoma. Gal-9 induced the apoptosis of Gal-9-sensitive GBC cells by increasing the levels of caspase-cleaved keratin 18 and phosphorylated p53. However, Gal-9 did not affect the expression of various cell cycle-related proteins. In addition, Gal-9 suppressed tumor growth by implanted human GBC cells in a xenograft model. Furthermore, Gal-9 induced the phosphorylation of the Ephrin type-B receptor, and the microRNA (miRNA) expression profile was markedly altered by Gal-9. Based on these results, various miRNAs might contribute to the suppression of tumor growth. Our data reveal that Gal-9 suppresses the growth of GBC, possibly by inducing apoptosis and altering miRNA expression. Thus, Gal-9 might serve as a therapeutic agent for the treatment of GBC.
 ...
PMID:Galectin-9: An anticancer molecule for gallbladder carcinoma. 2679 14

Biliary tract cancers (intrahepatic, perihilar and extrahepatic cholangiocarcinoma, and gallbladder and cystic duct cancers) are uncommon but highly lethal malignancies. Clinical presentation is often late, precluding curative surgical resection in most cases. For advanced disease, therapeutic options are limited to systemic chemotherapy, with suboptimal outcomes. An understanding of the molecular characteristics of biliary tract cancers may allow the clinical development of therapies targeting actionable alterations with the ultimate goal of improving clinical outcomes. We present a comprehensive review of biliary tract cancer genomics and their clinical implications. Alterations in genes in the EGFR-MAPK-PI3K pathway are seen most often. KRAS alterations are highly prevalent; BRAF alterations are mutually exclusive from RAS alterations and much less frequent. PIK3CA alterations are seen mostly in extrahepatic cholangiocarcinoma and gallbladder cancers whereas HER2 amplification is most common in gallbladder cancers. Various tumor suppressor genes, such as TP53 and p16 are also altered often in biliary tract cancers; however, agents to "activate" silenced genes are currently lacking. FGF and IDH pathway alterations are potential targets for therapeutic agents. FGF alterations are typically fusions with other genes, resulting in altered proteins, and are seen most often in intrahepatic cholangiocarcinoma. IDH pathway alterations affect cellular enzymatic processes and are most common in intrahepatic cholangiocarcinoma. Ongoing clinical trials of agents targeting these pathways hold the promise of improving clinical outcomes.
 ...
PMID:Molecular characteristics of biliary tract cancer. 2782 38


<< Previous 1 2 3 Next >>