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)

We analysed diagnostic phase plasma levels of thymidine kinase (TK) and mutated p53 in 81 patients with malignant lymphoma. Forty-three (53%) patients had increased (> 10 U/l) TK activity whereas 30 (37%) were positive for the mutated p53 gene product. In general, patients with p53 mutation positive tumors tended to have higher TK activity than those without. Furthermore, patients with high-grade non-Hodgkin's lymphoma (NHL) showed almost a linear correlation (rs = 0.79) between plasma levels of mutated p53 and TK. We conclude that the monoclonal antibody assisted detection of mutated p53 gene product may prove a useful adjunct to the diagnostic procedures of malignant lymphomas.
 ...
PMID:Evaluation of plasma levels of thymidine kinase and mutated p53 in 81 patients with newly diagnosed malignant lymphoma. 830 26

We have investigated the immunohistochemical expression of p53 protein in 96 cases of non-Hodgkin's lymphoma using a panel of five antibodies. Positive neoplastic cells were found in 30 (31.2%) cases, which could be divided into two groups according to their patterns of reactivity with the different antibodies; i.e. those positive with both polyclonal and monoclonal antibodies, and those which were stained only by monoclonal antibodies PAb1801 and/or PAb240. Positivity was nuclear in all but six cases in which cytoplasmic staining was found. In view of the hypothesis recently raised that p53 protein induces apoptosis we have compared our results with parallel staining for bcl-2 protein since bcl-2 is believed to be important, at least in lymphomas, in suppression of apoptosis. Staining for bcl-2 protein was performed on 83 cases and it was shown that p53-positive cases accounted for 10 out of 17 (59%) of the bcl-2-negative lymphomas but only for 15 out of the 66 (23%) bcl-2-positive cases, suggesting a possible relationship between the expression of these two proteins. Thus, our data show that p53 protein is abnormally expressed in a substantial proportion of non-Hodgkin's lymphomas and bears a significant inverse relationship to bcl-2 protein expression. However the molecular basis of this expression remains to be elucidated.
 ...
PMID:Immunohistochemical detection of p53 and bcl-2 proteins in non-Hodgkin's lymphoma. 843 40

Mutations in the p53 tumor suppressor gene occur with a frequency of 12.5% in lymphoid malignancies. The viral-associated diseases, Adult T-cell Leukemia (ATL) and Burkitt's lymphoma, showed higher p53 mutation frequencies of 24% and 41%, respectively. Mutations occurred in the highly conserved regions of the p53 gene. Two new hot spots for mutation were noted in exon 7 at codons 239 and 245. The spectrum of p53 mutations differs among different cancers. Transition mutations occurring in colon and brain tumors also predominated in the majority of the lymphoid malignancies. However, B-cell chronic lymphocytic leukemia (B-CLL) and non-Hodgkin's lymphoma (NHL) had an unusually high frequency of G to T transversions. Among carcinomas of the lung, liver, breast and esophagus there is also a high frequency of G to T transversions. The differences in mutation spectra between different lymphoid diseases may be due to differences in mutagenic factors or differences in the biological properties of the p53 protein in different lymphoid compartments. Mutation of the p53 gene is associated with advanced stage of lymphoid disease and poor prognosis. For B-CLL disease, p53 mutations are associated with drug resistance. Overexpression of the bcl-2 protein is also associated with a block in apoptosis. Resistance to apoptosis could be a general mechanism for drug resistance in B-CLL and other lymphoid diseases.
 ...
PMID:P53 gene mutations in lymphoid diseases and their possible relevance to drug resistance. 858 Jul 89

Although p53 mutations have been described frequently in high-grade B-cell non-Hodgkin's lymphoma (NHL), they have only been reported occasionally in low-grade NHL. We therefore describe clincobiologic and molecular genetic findings in two patients with p53 mutations and leukemic mantle cell lymphoma featuring an unusually aggressive course. Circulating malignant cells showed irregularity of nuclear outline with frequent deep clefts in both cases. Immunologic studies of neoplastic cells from peripheral blood samples and from cells obtained from an involved lymph node showed a mantle B-cell phenotype (CD5+, CD19+, CD22+, CD23- or weakly+ and bright expression for surface immunoglobulins). Malignant cells were shown to be hyperdiploid by cytofluorimetric study of DNA content and the presence of the t(11;14)(q13q32) was documented in one case. An altered electrophoretic mobility of p53 exon 5 was seen in both cases, with a missense mutation at codon 158 present in one case and a CAG to TAG mutation resulting in a 167-stop codon present in the second case. The percent of reactive cells with the 1801 monoclonal antibody detecting an epitope of the p53 was 37% in one case and 1% in the second case, supporting the notion that immunologic overexpression cannot be used for a selection criterion for the detection of p53 mutations. From these findings and from data available in the literature the conclusion can be drawn that p53 gene mutations at codons 158 and 167 may be associated with lymphoproliferative disorders and that low- or intermediate-grade NHL, including leukemic mantle cell lymphoma, may frequently carry this genetic change.
 ...
PMID:p53 exon 5 mutations in two cases of leukemic mantle cell lymphoma. 860 36

p53, a tumor suppressor gene, is frequently mutated in sporadic human cancer, and inherited mutations in p53 predispose to the early onset of cancer. p53 mutations occur frequently in sporadic lymphoma, and, in mice deficient for p53, lymphoma is the most common type of malignancy. Families with an increased incidence of lymphoma have been described, suggesting an inherited predisposition to lymphoma in these circumstances. To determine whether the predisposition to lymphoma in these families results from germline mutations in p53, we analysed exons 4-11 of the p53 gene in 35 individuals from 19 lymphoma-prone kindreds. We found no germline p53 mutations in any of the individuals tested. However, p53 expression assessed by immunohistochemistry, which suggests mutation, was observed in 35% of the tumor samples from the familial Hodgkin's disease cases and in 13% of the familial non-Hodgkin's lymphoma cases. These results suggest that p53 mutations do not play a critical role in heritable susceptibility to lymphoma. p53 may act by different, non-mutation related mechanisms in this setting, or be involved in late events in the pathogenesis of these tumors.
 ...
PMID:Absence of germline p53 mutations in familial lymphoma. 863 26

Mutations of the p53 tumor suppressor gene have been described in several subtypes of non-Hodgkin's lymphoma, but the incidence of p53 mutations in mantle cell lymphoma (MCL) is unknown. We hypothesized that cases of MCL with a variant or high-grade cytology would have a higher likelihood of p53 mutations than typical MCL. We were also interested in the prognostic significance of p53 mutations in MCL. Therefore, a series of 53 well-characterized cases of MCL with DNA from 62 tissue samples were analyzed by the polymerase chain reaction with denaturing gradient gel electrophoresis for exons 5-8 of p53. Immunoperoxidase studies with the antibody DO-7 to p53 protein were also performed on frozen sections. We found mutations of the p53 gene in 8 of the 53 cases (15%) of MCL. Missense mutations predominated, and 50% of the mutations occurred at known p53 hotspot codons. Of 21 cases with variant cytology (ie, anaplastic or blastic), 6 (28.6%) had p53 mutations as compared with only 2 of 32 cases (6.3%) with typical MCL cytology (P = .05), and p53 mutations preceded the development of variant cytology in 2 patients. Overexpression of p53 protein was observed in 6 of the 8 cases (75%) with p53 mutations and in none of the 45 wild-type cases. The median survival of the cases with mutant p53 was only 1.3 years (all died), whereas the median survival of cases with germline p53 was 5.1 years (P = .023). These results suggest that mutations of p53 may be one mechanism involved in the development of variant forms of MCL and indicate that p53 mutations in MCL predict a poor prognosis.
 ...
PMID:p53 mutations in mantle cell lymphoma are associated with variant cytology and predict a poor prognosis. 863 89

Tumor biopsies (paraffin embedded tissue) obtained from 45 Saudi patients with non-Hodgkin's lymphoma (NHL) were examined for the incidence of p53 mutations screened by polymerase chain reaction (PCR) and single strand conformation polymorphism (SSCP) analysis. DNA sequencing was carried out to confirm the occurrence of p53 mutation in PCR products showing abnormal migration by SSCP analysis. Only 1/45 samples showed the incidence of a homozygous mutation at codon 179 (exon 5) of the p53 gene that replaces histidine with tyrosine. The data showed that the frequency of p53 mutations was very low in Saudi NHL. Our results are consistent with the general observation that the p53 mutation is rather infrequent in hematopoietic malignancies like NHLs.
 ...
PMID:Studies of the p53 gene mutation in Saudi non-Hodgkin's lymphoma. 866 92

The expression of the apoptosis-regulating genes Bcl-2, Bcl-x, Bax, Mcl-1, and p53 analyzed in 4 cases of human immunodeficiency virus (HIV)-associated Hodgkin's disease, in 36 cases of HIV-related non-Hodgkin's lymphomas (NHLs), and in 109 cases of non-HIV-related NHLs by using immunohistochemistry. HIV-associated Hodgkin's disease samples were positive for all markers. For the HIV-related NHL samples, 36, 66, 88, 100, and 94% of the cases were Bcl-2, Bcl-x, Bax, Mcl-1, and p53 were found to be expressed in 69, 65, 82, 83, and 42%, respectively. No significant differences were observed in Bax and Mcl-1 staining between HIV-unrelated NHLs of B cell and T cell types. In contrast, Bcl-2 was positive in 66/79 (83%) and 10/30 (33%) of B cell and T cell HIV-unrelated NHLs, respectively (P2 < 0.001). Peculiar patterns were observed for hairy cell leukemia (Bax+, Bcl-2+, Mcl-1-) and for anaplastic large cell lymphoma (Bax+, Mcl-1+, Bcl-2-) in HIV-unrelated NHLs. Of interest, all cases with a positive expression of Bax were also found to express either Mcl-1 and/or Bcl-2, suggesting that Mcl-1 and Bcl-2 may counteract the pro-apoptosis function of Bax in vivo by protein-protein interaction within the tumor cell, as demonstrated previously in vitro. These results suggest that apoptosis regulation may have a role in the pathogenesis of some HIV-related and HIV-unrelated NHLs.
 ...
PMID:Immunodetection of apoptosis-regulating proteins in lymphomas from patients with and without human immunodeficiency virus infection. 868 41

The majority of low grade non-Hodgkin's follicular lymphoma undergo clinical progression to intermediate and high grade lymphoma, but the molecular mechanisms involved in this transformation are not yet well understood. In this article, we describe the case of a 66 year old man with follicular non-Hodgkin's lymphoma (NHL), in whom a centroblastic leukaemic transformation led to death in six months, despite a transient period of remission. At the time of transformation, cytogenetic analysis revealed the original coexistence of t(14;18)(q32;q21) and t(8;22)(q24;q11). These results were confirmed by fluorescent in situ hybridization, while molecular analysis showed a BCL2-JH rearrangement but failed to detect a c-myc rearrangement or any additional p53 mutation. Our observations would therefore suggest other mechanisms to be involved in the transformation of follicular NHL.
 ...
PMID:Transformation of follicular lymphoma with both t(14;18) and t(8;22). 890 4

The t(9;14)(p13;q32) translocation is associated with approximately 50% of lymphoplasmacytoid lymphoma (LPL), a subtype of B-cell non-Hodgkin's lymphoma (NHL). We cloned the chromosomal breakpoint of der (14) from an LPL case (1052) and showed that it involved a junction between 9p13 and the switch micro region of the Ig heavy chain locus (IgH) on 14q32. Using a YAC contig spanning 1.5 megabase (Mb), we determined that the 9p13 breakpoint in one case (1052) mapped within a 270-kb restriction fragment containing two previously reported 9p breakpoints associated with a alpha-heavy chain disease case (MAL) and KI-1 positive diffuse large cell lymphoma (DLCL) cell line (KIS-1). The same fragment also contained the PAX-5 gene which encodes a B-cell specific transcription factor involved in the control of B-cell proliferation and differentiation. The breakpoints of KIS-1 and 1052 were mapped within the 5' noncoding region of PAX-5, while the 9p13 breakpoint of MAL mapped 230 to 270 kb upstream to PAX-5. In all three cases, the translocation caused the juxtaposition of the PAX-5 gene to the IgH locus in the opposite direction of transcription. When compared with six other DLCL cell lines lacking t(9;14)(p13;q32), the KIS-1 cell line showed an 11-fold overexpression of PAX-5 mRNA and a significantly reduced expression of the p53 gene, which is normally regulated by PAX-5. Moreover, metaphase and interphase fluorescence in situ hybridization (FISH) analysis using a YAC clone spanning 1 Mb including the PAX-5 as a probe identified chromosomal translocations in 5 of 7 cases carrying 9p13 translocations. These findings suggest that the PAX-5 gene is the target of the t(9;14) in LPL whereby its expression may be deregulated by juxtaposition to IgH regulatory elements, thus contributing to lymphomagenesis.
 ...
PMID:The t(9;14)(p13;q32) chromosomal translocation associated with lymphoplasmacytoid lymphoma involves the PAX-5 gene. 894 44


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>