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)

The pathogenesis of gastric mucosa-associated lymphoid tissue (MALT) lymphoma is an intriguing issue and is thought to be closely related to Helicobacter pylori infection. Gastric MALT lymphoma is thought to progress from the reactive state to low-grade malignancy and sometimes to high-grade malignancy. In the present study, we examined immunohistochemically the expression of bcl-6 and p53 proteins in gastric MALT and gastric diffuse large lymphoma without low-grade MALT lymphoma component (gastric DLL) to elucidate their role in high-grade transformation of low-grade MALT lymphoma. We detected bcl-6 protein only in the high-grade components in four of eight high-grade MALT lymphoma cases and in four of six gastric DLL cases. In contrast, none of 17 cases of low-grade MALT lymphoma expressed bcl-6 protein (P < .05). p53 protein was detected in the high-grade components in 6 of 8 high-grade MALT lymphoma cases and in 4 of 6 gastric DLL cases, but it was expressed in 2 of 17 cases of low-grade MALT lymphomas. All high-grade gastric MALT lymphomas cases were positive for p53 protein and/or bcl-6 protein. There is a tendency for an inverse relationship between bcl-6 protein and p53 protein. These findings suggest that high-grade transformation of gastric low-grade MALT lymphoma is associated with overexpression of p53 or bcl-6 protein.
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PMID:bcl-6 protein is identified in high-grade but not low-grade mucosa-associated lymphoid tissue lymphomas of the stomach. 950 89

Hepatitis C virus (HCV) infection may be complicated by non-Hodgkin's lymphoma. We describe eight cases of B-cell extranodal non-Hodgkin's lymphoma occurring during the course of chronic HCV-related hepatic disease (low-grade of mucosa-associated lymphoid tissue [MALT]-type; diffuse large cell; Burkitt; diffuse small cell). Some were localized to the liver (2), liver and spleen (1), spleen (1), peritoneal cavity (1), parotid gland (1); others manifested in the nasopharynx (1) and eyelid (1) but were accompanied by nodal disease. Four lymphomatous specimens available for molecular analysis exhibited clonal immunoglobulin gene rearrangements, lacked bcl-2, bcl-6, c-myc genes and p53 alterations, and did not contain replicative intermediate HCV RNA, as documented by a strand-specific reverse transcriptase-polymerase chain reaction. Low levels of positive-strand HCV RNA were detected in a single hepatic lymphoma, suggesting the presence of the virus in residual hepatocytes. The antigen-driven properties of HCV-associated B-cell malignant neoplasms may be considered for hepatic MALT-type lymphoma, which probably originated from lymphoid tissue acquired during long-standing HCV infection.
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PMID:Extranodal lymphomas associated with hepatitis C virus infection. 957 65

We studied overexpression of p53, Bcl-2, Bcl-6, c-Myc and Mdm2 proteins by immunohistochemistry for a total of 27 primary central nervous system B cell lymphomas (CNS lymphomas) in immunocompetent patients and one CNS lymphoma in an AIDS patient. The expression of Epstein-Barr (EB) virus-encoded small RNA-1 (EBER-1) was also analysed using in situ hybridisation. Overexpression (more than 20% of cells stained) of p53 protein was detected in 8 of 27 immunocompetent cases (30%); 6 cases showed a nuclear stain and 2 cases showed cytoplasmic stain (nuclear exclusion). Strong Bcl-2 or Bcl-6 immunoreactivity suggestive of overexpression was seen, respectively, in 5 (19%) and 6 (22%) cases; 2 cases were positive for both immunoreactivities. Interestingly, overexpression of Bcl-2 or Bcl-6 was not seen in the cases which showed p53 overexpression (P < 0.03; chi-square test). EBER-1 expression was not detected in any of the 27 immunocompetent cases, but was found in the AIDS-related CNS lymphoma, which also showed an overexpression of Bcl-6, but not Bcl-2. None of the cases showed c-Myc or Mdm2 overexpression. Taken together, it is suggested that CNS lymphoma in immunocompetent hosts is a distinct disease that has a different molecular profile from those of systemic lymphoma and/or AIDS-related CNS lymphoma.
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PMID:Expression of oncogenic molecules in primary central nervous system lymphomas in immunocompetent patients. 960 May 97

Gastric low-grade mucosa-associated lymphoid tissue (MALT) lymphoma is a unique disease. A vast majority of lymphoma cells are centrocyte-like cells or resemble monocytoid B cells, and occasionally show plasmacytic differentiation. Immunophenotypical and immunogenotypical examinations have indicated that they are in the differentiation stage of memory B cells, whose normal counterparts are marginal zone lymphocytes or monocytoid B cells in the lymphoid tissues. It arises from chronic gastritis closely associated with Helicobacter pylori (H. pylori) infection. Mucosa-associated lymphoid tissue lymphomas of other organs are also based on acquired MALT associated with chronic inflammation or autoimmune diseases. Interestingly, the majority of gastric low-grade MALT lymphomas regress by the eradication of H. pylori. The lymphoma cells, however, are not derived from B cells reacting with H. pylori itself but from autoreactive B cells. Although the mechanism of their oncogenesis has not been clarified, previous data suggest that autoreactive B cells proliferate in response to H. pylori-specific T cells, presumably with some cytokines. The genetic instability of such B cells then induces chromosomal abnormalities including trisomy 3 and/or other genetic changes. These B cells have the ability of autonomic proliferation and, even so, they might be sensitive to T cell stimuli. Low-grade gastric lymphomas occasionally progress to high-grade malignancy. The high-grade component of MALT lymphomas are composed of large-sized lymphoma cells that are morphologically indistinguishable from nodal large B cell lymphomas. This high-grade transformation is associated with p53 abnormalities or Bcl-6 overexpression. Gastric MALT lymphoma may provide a useful model in understanding multistep lymphomagenesis.
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PMID:Gastric low-grade mucosa-associated lymphoid tissue lymphomas: their histogenesis and high-grade transformation. 970 38

Primary mediastinal B-cell lymphoma (PMBL) shows chromosome 9p anomalies in 50% of cases. Based on reports that p16INK4A gene, located on this chromosomal arm, is frequently altered in aggressive lymphomas, we analysed for alterations of this gene in 27 cases of PMBL, which were part of a series of 32 PMBL cases that have been characterized for alterations in c-myc, p53, N-ras, bcl-1, bcl-2, bcl-6 and for Epstein-Barr virus (EBV) infection. Four cases showed p16INK4A gene anomalies, including three with promoter methylation and one homozygous deletion. Eight PMBLs showed c-myc rearrangements. Three additional cases showed sequence variations in the c-myc P2 promoter, two of which consisted of the same germline variation involving a novel polymorphic XhoI site. Four tumours contained p53 gene mutations and three had clonal EBV infection. One case had a bcl-6 rearrangement. In conclusion, our study shows that p16INK4, c-myc and p53 alterations occur in 15%, 25% and 13% of PMBLs, respectively. EBV monoclonality was found in 9% of cases, whereas no abnormality was detected in bcl-1, bcl-2 and N-ras. Thus, none of the common genetic aberrations seen in other types of non-Hodgkin's lymphomas appears to be stringently involved in the pathogenesis of this unique lymphoma type.
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PMID:Molecular features of primary mediastinal B-cell lymphoma: involvement of p16INK4A, p53 and c-myc. 1052 30

The aim of this study was to assess the clinical significance and potential prognostic value of the expression of a panel of surface markers, proliferating, suppressor and oncogenic proteins in diffuse large B-cell lymphomas (DLBCL). Biopsies were collected from 158 patients with DLBCL and analyzed immunohistochemically for p53, p21/WAF1, bcl-2, cyclin-D1, bcl-6, mdr, CD5, CD30, epithelial membrane antigen (EMA), Ki-67 and c-myc positive tumor cells. Among these, 76 young and middle-aged patients (20-65 years) were selected to investigate the relationship between protein expression, clinical features, and survival. Survival analysis showed that advanced stage, high lactic dehydrogenase level, and high International Prognostic Index (IPI) were poor prognostic factors associated with a shorter overall survival (OS) and disease-free survival (DFS) times. A high p53 expression and low bcl-6 expression were associated with a shorter DFS time. The histological variant type, cyclin-D1+ CD5+ DLBCL, positive epithelial membrane antigen (EMA+) CD30- DLBCL, high bcl-2 expression, and low Ki-67 proliferation activity tended to be associated with worse survival, but the correlations were not statistically significant. In the multivariate analysis, the most significant factors were age, followed by IPI and last p53. The expression of p21/WAF1, mdr, and c-myc proteins did not influence OS and DFS. The expression of p53 and bcl-6 proteins may be useful prognostic indicators in DLBCL. Cyclin-D1+ CD5+ or EMA+ CD30- DLBCL tended to predict a worse survival and may probably bear a significant prognostic value worthy of consideration. Overall, clinical factors appeared to be more important than biologic parameters in determining the prognosis of diffuse large B-cell lymphomas.
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PMID:Prognostic clinicopathologic factors, including immunologic expression in diffuse large B-cell lymphomas. 1063 24

We performed a retrospective immunohistochemical study of the relationships between clinical manifestations and outcomes of diffuse large B-cell lymphoma (DLBCL) and expression of oncogenic proteins in 21 cases of DLBCL at various clinical stages. Cases of nodal origin expressed p53 more often and presented with high clinical stage more frequently than those of extranodal origin. Expression of c-Myc or p53, but not Bcl-6, Bcl-2, or Bcl-1, showed a statistically significant positive correlation with high clinical stage at presentation and with high or high-intermediate risk. Coexpression of c-Myc and p53 occurred in 7 of 12 patients with high clinical stage but was absent in patients with low clinical stage; coexpression was more frequent in patients with high or high-intermediate risk than in patients with low or low-intermediate risk. Four patients with this coexpression pattern demonstrated an unusually aggressive clinical course (median survival, 7 months). Coexpression of c-Myc and p53 seems to be a better indicator than the MIB1 proliferative index for identification of a cohort of aggressive disease in patients with DLBCL.
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PMID:Expression of c-Myc and p53 correlates with clinical outcome in diffuse large B-cell lymphomas. 1133 87

PC SPES (BotanicLab, Brea, California) an herbal supplement for patients with prostate cancer, is composed of 7 highly concentrated Chinese herbs and 1 US herb. It was developed in seeking positive attributes of Chinese and Western medicine for cancer treatment. Chemical standardization of this composition showed that baicalin is the most abundant active compound. Several reports on phase 2 clinical studies of PC SPES suggest that it is a well-tolerated active treatment for androgen-independent prostate cancer. In this report, data obtained from various laboratory experiments will be presented to elucidate the in vitro mechanism. Profound biologic effects of PC SPES on prostate cancer cells were observed on both androgen-dependent (LNCap) and androgen-independent (DU-145) cell lines. These effects include the following: (1) induction of cell apoptosis and cell cycle modulation; (2) inhibition of cell proliferation; (3) downregulation of bcl-2, bcl-6, proliferating cell nuclear antigen, and prostate-specific antigen proteins; (4) downregulation of androgen receptor (AR); and (5) upregulation of p53, bax, and p21 proteins. Concurrent animal studies using 2 different models, Copenhagen rats and nude mice, confirmed a dose-dependent suppressive effect of PC SPES on tumor volumes and tumor progression. Our results show that the cytotoxic and cytostatic properties of PC SPES are not entirely dependent on the presence of AR. The antitumor mechanism of PC SPES is complex. It involves multiple metabolic pathways, such that the whole extract acts on redundant mechanisms, which otherwise will permit cell survival if a single-target agent is used.
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PMID:In vitro mechanism of PC SPES. 1150 43

Only a few reports have been published on molecular genetic alterations in primary central nervous system lymphomas (PCNSLs) of the diffuse large B-cell type and no reports have addressed the correlation between the genetic alterations and clinical course of the patients with this neoplasm. Thus, the molecular background of the PCNSL and its importance for the clinical course of the patients are still unclear. We investigated a series of 14 patients with PCNSL to determine structural alterations of the INK4a/ARF, MDM2, and TP53 genes, the status of bcl-2 and bcl-6 protein expression, and the clinical course of the patients (i.e. their survival time after diagnosis). No structural alterations of MDM2 and TP53 genes were found. Only INK4a/ARF genes whose expression affects both the p161NK4a-Rb and p14ARF-mdm2-p53 pathways in the regulation for cell cycle and apoptosis, showed an alteration of the homozygous deletions at a high frequency (nine of 14 patients: 64%). This specific alteration was not related with the bcl-6 expression, but a relation was shown with overexpression of the bcl-2 anti-apoptotic protein (p = 0.036, chi-square test), as well as a shorter patient survival (p = 0.044, Wilcoxon test). There was only a tendency, not a significant correlation, in which the patients with bcl-2 overexpression resulted in poor prognosis (p = 0.149). The present study is the first to suggest that the INK4a/ARF gene homozygous deletions and overexpression of the bcl-2 protein may be correlated with each other and together serve as important predictors for the prognosis of patients with PCNSL.
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PMID:Homozygous deletion of INK4a/ARF genes and overexpression of bcl-2 in relation with poor prognosis in immunocompetent patients with primary central nervous system lymphoma of the diffuse large B-cell type. 1180 83

The International Prognostic Index (IPI) identifies poor- and good-risk patients with diffuse large B cell lymphoma (DLBCL); however, the majority of patients have an intermediate IPI, with an uncertain prognosis. To determine whether cellular factors can be combined with the IPI to more accurately predict outcome, we have analyzed 177 presentation nodal DLBCLs for the expression of bcl-2 and a germinal center (GC) phenotype (defined by expression of bcl-6 and CD10). P53 gene band shifts were detected using single-stranded conformational polymorphism polymerase chain reaction analysis of exons 5-9 and were correlated with protein expression. In a Cox regression analysis, IPI (R = 0.22, P <.0001) and bcl-2 (R = 0.14, P =.0001) were independent poor prognostic factors and a GC phenotype predicted a favorable outcome (R = -0.025, P =.02). Neither p53 expression nor band shifts had a significant effect on survival. Using the IPI alone, 8% of patients were identified as high risk. Expression of bcl-2 in the intermediate IPI group identified a further 28% of patients with an overall survival comparable to the high IPI group. In the intermediate IPI, bcl-2(-) group, the presence of a GC phenotype improved overall survival to levels approaching the IPI low group. Following this analysis only 15% of patients failed to be assigned to a favorable- or poor-risk group. Sequential addition of bcl-2 expression and GC phenotype into the IPI significantly improves risk stratification in DLBCL. For the 36% of high-risk patients with a 2-year overall survival of 19%, alternative treatment strategies should be considered in future trials.
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PMID:Germinal center phenotype and bcl-2 expression combined with the International Prognostic Index improves patient risk stratification in diffuse large B-cell lymphoma. 1183 Apr 58


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