Abstracts from the sixth meeting of the international association of pancreatology, November 2–4, 1994, Chicago, IL (original) (raw)
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Evaluation of the pattern and prognostic implications of anti-p53 in hepatocellular carcinoma
Introduction: The p53 antigen is oncoprotective and when damaged, leads to production of anti-p53. It also predisposes to various cancers , including hepatocellular carcinoma (HCC). Serum anti-p53 has been proven to have prognostic and other values in patients with HCC. The objectives of this study were to determine the serum pattern, prevalence, diagnostic and prognostic utility of serum anti-p53 in Nigerians with HCC.
The p53 Tumor Suppressor Gene: From Molecular Biology to Clinical Investigation
Annals of the New York Academy of Sciences, 2006
The tumor suppressor p53 is a phosphoprotein barely detectable in the nucleus of normal cells. Upon cellular stress, particularly that induced by DNA damage, p53 can arrest cell cycle progression, thus allowing the DNA to be repaired; or it can lead to apoptosis. These functions are achieved, in part, by the transactivational properties of p53, which activate a series of genes involved in cell cycle regulation. In cancer cells bearing a mutant p53, this protein is no longer able to control cell proliferation, resulting in inefficient DNA repair and the emergence of genetically unstable cells. The most common changes of p53 in human cancers are point missense mutations within the coding sequences of the gene. Such mutations are found in all major histogenetic groups, including cancers of the colon (60%), stomach (60%), breast (20%), lung (70%), brain (40%), and esophagus (60%). It is estimated that p53 mutations are the most frequent genetic event in human cancers, accounting for more than 50% of cases. One of the most striking features of the inactive mutant p53 protein is its increased stability (half-life of several hours, compared to 20 min for wild-type p53) and its accumulation in the nucleus of neoplastic cells. Therefore, positive immunostaining is indicative of abnormalities of the p53 gene and its product. Several studies have shown that p53 mutations are associated with short survival in colorectal cancer, but the use of p53 as a tumoral marker is still a matter of debate.
p53 Antibodies as a Diagnostic Marker for Cancer: A Meta-Analysis
Molecules
Importance: The protein p53 is an unequivocal tumor suppressor that is altered in half of all cancers. The immune system produces systemic p53 autoantibodies (p53 Abs) in many cancer patients. Objective: This systemic review and meta-analysis focuses on the prognostic value of p53 Abs expressed in the serum of patients with solid tumors. Data Sources: All the clinical investigations were searched on PubMed from the first study dated 1993 until May 2021 (date of submission of the manuscript). Study Selection: Studies were included that met the following criteria: 1) participants with cancer; 2) outcome results expressed in relation to the presence of a p53 antibody; 3) a primary outcome (disease-free survival, overall survival or progression-free survival) expressed as hazard ratio (HR). The following exclusion criteria were used: 1) insufficient data available to evaluate outcomes; 2) animal studies; 3) studies with less than 10 participants. As a result, 12 studies were included in...
Clinical Biochemistry, 2008
Objective: p53 antigen is an oncoprotective antigen and when damaged, leads to production of anti-p53 and also predisposes to various cancers, including hepatocellular carcinoma (HCC). Serum anti-p53 has been proven to have a prognostic value in patients with HCC. The objective of this study was to determine the prevalence and prognostic utility of serum anti-p53 in Egyptian patients with HCC. Methods: Forty one patients with HCC, 26 patients with liver cirrhosis and 29 healthy controls were included in this study. For all the studied groups, we studied the clinical data, abdominal ultrasound (US) findings, biochemical liver function tests, serum alpha-fetoprotein (AFP) levels detected by enzyme immunoassay (EIA) kit and anti-p53 antibody levels by a modified enzyme-linked immunosorbent assay (ELISA). The severity of liver disease was assessed by Child-Pugh and MELD scores. Tumor characteristics were detected by (US) with or without computed tomography (CT) scan. These characteristics included tumor size, number and site. Tumor staging was done using Okuda, Cancer Liver Italian Program (CLIP) and Tokyo staging systems. Also, the overall survival of patients with HCC with reference to p53 antibody level was studied. Results: The mean age of HCC patients was 57.95 ± 8.41. There was a male predominance among HCC patients with male-to-female ratio of 3.6:1. Anti-p53 antibodies were detected in the sera of 68.3% of HCC patients, 50% of liver cirrhosis patients and 17.2% of healthy control subjects. The data showed that HCC patients had a significantly higher mean anti-p53 antibody values (p = 0.0001), than both liver cirrhosis patients and healthy control groups. Our results revealed that anti-p53 has a positive significant correlation with AFP (p = 0.002), severity of liver disease [Child Pugh score (p = 0.02) and MELD score (p = 0.0003)], tumor size (p b 0.0001), tumor number (p = 0.003) and tumor staging systems [Okuda (p = 0.04), CLIP (p = 0.006) and Tokyo (p b 0.0001)]. Also, our results revealed that serum anti-p53 antibodies had a significant association with overall survival of patients with HCC (p = 0.019) with a shorter survival time in anti-p53 positive status patients and with higher anti-p53 antibody levels within 19 months follow up. Conclusion: The detection of anti-p53 antibodies may be suitable for assessing the prognosis of HCC patients. The higher percentage of positivity of anti-p53 antibodies in Egyptian control subjects than reported elsewhere needs further thorough investigation.
Bulletin du cancer
p53 was originally considered to be a nuclear oncogene, but several convergent lines of research have indicated that the wild-type gene functions as a tumor suppressor gene negatively regulating the cell cycle. Mutations in the p53 gene have been detected in many tumor types and seem to be the most common genetic alterations in human cancer. In this preliminary study, sera of 92 patients (pts) with breast disease were analyzed for the presence of the mutant p53 protein (m p53) with a selective immunoenzyme assay employing a monoclonal antibody (PAb 240) specific for the majority of mammalian m p53 but not for the wild-type protein. Of the 10 patients with benign breast disease, only two (20%) showed detectable m p53 levels in the serum. In the breast cancer group, sera from 7 of the 30 pts (23%) without lymph node involvement were positive for m p53, as were 7 out of the 45 pts (15%) with metastatic lymph nodes and I out of the 7 pts (14%) with disseminated disease. The specifity of m p53 assay evaluated in 20 healthy 26 MicelU et al.
Prevalence of serum antibodies against the p53 tumor suppressor gene protein in various cancers
International Journal of Cancer, 1994
We have developed 2 new quantitative methods for measuring anti-p53 antibodies in human serum. Using these methods we analyzed 1,392 sera from patients with various malignancies and 230 sera from individuals without malignancy. Highest prevalence of antbps3 antibodies was associated with ovarian and colon cancers ( I 5%), followed by lung (8%) and breast (5%) cancers. Prevalence in other malignancies was lower (<4%). In hospitalized patients and apparently healthy individuals, prevalence was very low (<2 and I O/ o respectively). Extremely high antibody concentrations (> lo5 U/L) were found in 5 ovarian, 2 breast, I lung and I colon cancers. Sequential analysis of 6 positive samples has shown that the p53 antibody test may have potential for patient monitoring. The p53 antibody-positive sera from breast cancer patients were associated with tumors that were steroid hormone receptor-negative (p < 0.002). We propose that the measurement of p53 antibodies is a relatively specific serological test for cancer, which can be performed with easily automatable and quantitative methodologies and may be further exploited for patient monitoring, prognosis, diagnosis and probably screening for selected cancers.
BioEssays, 1995
p53 is a multifunctional protein which plays a role in modulating gene transcription, policing cell cycle checkpoints, activating apoptosis, controlling DNA replication and repair, maintaining genomic stability and responding to genetic insults. Mutation of the p53 gene confers the single greatest known selective advantage favoring cancer formation. Point mutations result not only in the loss of tumor suppressor functions, but also in the gain of tumor promotion functions. These dual circumstances may be unique to p53 and, in part, could explain the relatively powerful force behind this selection pressure. General mechanisms of gain of function by mutated p53 may include alteration in transcriptional modulation and newly acquired targets for transcriptional regulation and protein binding. Despite the direct significance of p53 mutations, loss of the remaining wild-type allele is usually required for the formation of tumors in the natural setting. Novel applications of the basic scientific knowledge of p53 could lead to an improvement in cancer treatment, hopefully in the not so Accepted
What do we need to know and understand about p53 to improve its clinical value?
The Journal of Pathology, 2021
Few proteins are more studied than the p53 tumour suppressor, but what have we learned from these studies and what do we really know about p53 that can benefit clinical practice? The DNA sequence encoding p53 is frequently mutated in cancers but the functional outcomes of single mutations, in respect to loss or gain of different activities, especially in relation to immune evasion, are not clear. This illustrates p53's complexity which even after 40 years keeps providing surprises, but also explains why it has not yet lived up to its potential to benefit cancer treatment. We have reassessed a few key experiments that shaped the p53 field and we take a closer look at the interpretations of these experiments: what they have taught us, the resulting dogmas, and their potential clinical importance. One outcome is a more dynamic view of p53 in terms of its activity, its regulation, and downstream effectors, which will benefit the clinical application of p53 for diagnosis, prognosis, and therapy. Mutations and regulatory factors can have different effects on p53 activity depending on context, important but neglected aspects when interpreting p53 and its pathways in cancers. Even though p53 is undoubtedly unique as a multifunctional hub in different cellular pathways, the concept of a factor taking up different functions within a regulatory pathway during different conditions is not. In this sense, p53 continues to lead the way for a better understanding of the cellular and molecular mechanisms underlying cancer development in vivo.