Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

P53 is a tumour suppressor gene, located in the short arm of chromosome 17, which encodes for a nuclear protein involved in the control of cellular growth, regulating the entry of the cell into the S-phase. P53 mutations have been identified in a progressively increasing number of human malignancies. Nuclear p53 protein is usually present in non-tumour cells in minute concentrations, due to its short half-life. In contrast, tumours with p53 mRNA mutations show a higher nuclear protein concentration, detectable by immunohistological techniques, due to stabilization by complexing with other proteins such as heat-shock protein or wild-type p53 protein. Levels of nuclear p53 protein detected by immunohistochemistry with the monoclonal antibody PAb 1801 were measured with the aid of an image analysis system in 83 non-Hodgkin's lymphomas (NHLs) and 13 cases of Hodgkin's disease, as well as in 14 cases of normal thymus, reactive tonsils, and lymphadenitis. High levels of p53 protein (greater than 5 per cent of the cells) were present only in high-grade lymphomas (in the proportion 13/55), with a peak incidence in Burkitt's lymphoma (5/8 cases). Lower levels (less than 5 per cent) of p53 protein were detected in low-grade B- and T-cell lymphomas, as well as in most of the cases of Hodgkin's disease, where p53 protein was selectively present in Hodgkin and Reed-Sternberg cells. In 5/14 reactive tonsils or lymph nodes, occasional p53-positive cells were identified. These results suggest a relationship between levels of p53 protein and the aggressiveness of NHL.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:P53 protein expression in lymphomas and reactive lymphoid tissue. 138 24

Lymphoid neoplasms, like all malignant tumors, arise as a consequence of the accumulation, in a single cell, of a set of genetic lesions that result in altered proliferation or increased clonal life span. The most frequently observed genetic abnormalities among the malignant non-Hodgkin's lymphomas are translocations, which appear to be lineage and, to a large extent, lymphoma specific. Recombinases that normally mediate the process of antigen receptor gene rearrangement appear to have an important (but not exclusive) role in the mediation of these translocations and of other types of gene fusion (e.g., deletion of intervening DNA). Frequently, such fusions result in the increased or inappropriate expression of crucially important proteins, many of which are transcription factors that regulate the expression of other genes. These abnormalities, however, do not appear to be sufficient to induce lymphoma, and it is likely that the additional genetic lesions required differ from one tumor to another. The likelihood of any given clone of cells accumulating a sufficient number of relevant genetic lesions to give rise to a lymphoma is probably a function of its life span. Prolonged survival of a cell clone may be mediated by viral genomes (e.g., Epstein-Barr virus and human T-cell leukemia/lymphoma virus type 1), by the abnormal expression of cellular genes that inhibit apoptosis (e.g., bcl-2), or by the mutation or deletion of cellular genes that are necessary for apoptosis, e.g., p53. The background rate at which genetic lesions occur is amplified by the interaction of inherited and environmental factors, the latter appearing to be the major determinant of incidence rates. However, inherited factors that influence lymphomagenesis, including variability in the ability to repair DNA damage or in the fidelity of antigen receptor recombinases for their signal sequences, may be crucial determinants of which particular individuals in a given environmental setting develop lymphoma.
 ...
PMID:Molecular basis of lymphomagenesis. 139 68

Mutation of the p53 protein may represent the commonest genetic event in human malignancy. Abnormal p53 expression has been reported in a variety of carcinomas, sarcomas and lymphoid neoplasms; however there is little information in relation to Hodgkin's disease. The expression of the nuclear phosphoprotein was investigated in paraffin-embedded biopsies from fifty patients with Hodgkin's disease using a polyclonal antibody, CM-1 and in snap-frozen material with monoclonal antibodies, PAb 1801 and PAb 240. Specifically, immunoreactivity was localised to the Reed-Sternberg cells or mononuclear variants in both nodular sclerosing (86% cases) and mixed cellularity (57% cases) subtypes of Hodgkin's disease. However, no positive staining was found in our cases of nodular lymphocyte predominant type Hodgkin's disease. Serial biopsies following recurrence of disease demonstrated consistent results. It is suggested that overexpression of p53, probably mutant, may have a role in the tumorigenesis of Hodgkin's disease.
 ...
PMID:p53 expression in Reed-Sternberg cells of Hodgkin's disease. 141 1

p53 is a tumor suppressor gene that commonly undergoes mutations in human tumors, including lymphomas. Because p53 mutations are not restricted to a single locus, immunohistochemistry is useful to detect p53 expression and correlate this finding with lymphoma phenotype. Cryostat sections from 125 cases of lymphoma were analyzed for p53 expression using three different monoclonal antibodies (pAb 421, 1801, 240) which react with human cellular p53 and a common conformational epitope on mutant p53. A control antibody (pAb 246) reacts only with wild type p53 of murine origin and was negative in all cases. Tissue from 29 cases of lymphoid hyperplasia, including six from human immunodeficiency virus-positive (HIV+) patients, were negative for p53. p53 was predominantly localized in nuclei of high-grade lymphomas, including 14 of 46 cases of B cell immunoblastic lymphomas and two of five T cell immunoblastic lymphomas. p53 expression was relatively common in lymphomas from HIV+ patients, and unusual in intermediate and low-grade lymphomas of follicular center cell type. Low-grade lymphoma of small lymphocytic type disclosed p53+ large cells (paraimmunoblasts) that may play a role in tumor progression in this lymphoma subtype. p53 was also strongly expressed in the nuclei of Reed Sternberg cells from 19 of 37 cases of Hodgkin's disease, including six cases of mixed cellularity, and 13 cases of nodular sclerosing type. Immunohistochemical staining is a rapid method to identify p53 expression in lymphomas.
 ...
PMID:Immunohistochemical analysis of p53 expression in malignant lymphomas. 146 98

Germline p53 mutations have been identified in the Li-Fraumeni syndrome but the role of such mutations in familial leukemia is not established. The p53 gene was examined by single-strand conformation polymorphism analysis of exons 4-8 in 10 families with multiple members affected with leukemia. The diagnoses included acute and chronic leukemias and Hodgkin's disease. Identified in two families were p53 mutations that were nonhereditary. These included a 2-bp deletion in exon 6 found in the lymphoblast DNA of one child whose sibling, cousin, and several adult relatives had acute leukemia. The other nonhereditary p53 mutation was a transition at codon 248 (CGG to CAG, arginine to glutamine) found in the lymphoblasts of a patient with a preleukemic syndrome and acute lymphoblastic leukemia (ALL) whose brother is a long-term survivor of ALL. Thus, p53 mutations were found to occur in two families but both were nonhereditary. Moreover, in the remaining eight families no p53 mutation was identified in the regions of p53 where most mutations have been found in other cancers. Although p53 mutations sometimes may be present, they do not appear to be a primary event responsible for hereditary susceptibility to familial leukemia. This study suggests involvement of other genes or mechanisms.
 ...
PMID:Absence of hereditary p53 mutations in 10 familial leukemia pedigrees. 164 30

The gene encoding p53 phosphoprotein, originally believed to be an oncogene, recently has been proposed as a candidate antioncogene (tumor-suppressor gene). Abnormalities of the p53 gene expression have been demonstrated in different human malignancies including carcinomas and sarcomas, but little information concerning p53 immunoreactivity in human lymphomas is so far available. In this study immunohistochemical staining for p53-protein was performed on frozen- and paraffin-embedded samples from patients with Hodgkin's (HD) and non-Hodgkin's lymphomas (NHL). No p53 immunoreactivity could be demonstrated in any cell type in nonneoplastic lymphoid samples, including germinal center cells in reactive lymph nodes and cortical thymocytes. On the other hand, a significant proportion of p53+ neoplastic cells was observed in 23 of 31 cases of HD and 17 of 68 cases of NHL. All positive lymphoma cases were diagnosed as high-grade or CD30+ anaplastic NHL. The demonstration of abnormal expression of p53 protein in these diseases can contribute to addressing unresolved issues regarding the origin and pathogenesis of HD and CD30+ anaplastic lymphomas.
 ...
PMID:Immunohistochemical evidence of abnormal expression of the antioncogene-encoded p53 phosphoprotein in Hodgkin's disease and CD30+ anaplastic lymphomas. 168 Jan 18

Programmed cell death is a physiological, energy-consuming mechanism leading to suicide of the cell. Cell death is accomplished by the activation of endonucleases that fragment the cell's nuclear DNA. Some tumour cells remain susceptible to programmed death. These are hormone- and growth factor-dependent tumour cells. Hormone or growth factor deprivation induces signals leading to apoptosis. Other tumours gain strong resistance to apoptosis. One of the normal functions of the bcl-2 gene is to provide longevity to memory B cells. When this gene becomes translocated in follicular B cell lymphomas, it renders lymphoma cells resistant to apoptosis. Latent membrane protein encoded by an EBV gene, either by itself or by amplifying bcl-2, enables tumour cells (nasopharyngeal carcinoma; Reed-Sternberg cell of Hodgkin's disease) to resist apoptotic death. Loss of antioncogene p53 provides for resistance against programmed cell death. Breakdown of resistance to apoptosis in tumour cells can be achieved by oncolytic viruses; generation of lymphotoxin and tumour necrosis factor; monoclonal antibodies; transfection with plasmid vectors carrying p53; gamma irradiation; and certain chemotherapeutic agents.
 ...
PMID:Programmed cell death (apoptosis): its virological and immunological connections (a review). 181 29

We have investigated the frequency of p53 mutations in B- and T-cell human lymphoid malignancies, including acute lymphoblastic leukemia, the major subtypes of non-Hodgkin lymphoma, and chronic lymphocytic leukemia. p53 exons 5-9 were studied by using genomic DNA from 197 primary tumors and 27 cell lines by single-strand conformation polymorphism analysis and by direct sequencing of PCR-amplified fragments. Mutations were found associated with (i) Burkitt lymphoma (9/27 biopsies; 17/27 cell lines) and its leukemic counterpart L3-type B-cell acute lymphoblastic leukemia (5/9), both of which also carry activated c-myc oncogenes, and (ii) B-cell chronic lymphocytic leukemia (6/40) and, in particular, its stage of progression known as Richter's transformation (3/7). Mutations were not found at any significant frequency in other types of non-Hodgkin lymphoma or acute lymphoblastic leukemia. In many cases, only the mutated allele was detectable, implying loss of the normal allele. These results suggest that (i) significant differences in the frequency of p53 mutations are present among subtypes of neoplasms derived from the same tissue; (ii) p53 may play a role in tumor progression in B-cell chronic lymphocytic leukemia; (iii) the presence of both p53 loss/inactivation and c-myc oncogene activation may be important in the pathogenesis of Burkitt lymphoma and its leukemic form L3-type B-cell acute lymphoblastic leukemia.
 ...
PMID:p53 mutations in human lymphoid malignancies: association with Burkitt lymphoma and chronic lymphocytic leukemia. 205 20

The expression of 20 proto-oncogenes was analysed by Northern blotting in four cell lines derived from patients with Hodgkin's disease (L428, L540, CO and DEV) and compared to lymphoid and myeloid leukemia cell lines and normal hematopoietic cells. Expression of the proto-oncogenes c-myc, p53, c-jun, pim-1, lck, c-syn, c-raf and N-ras were detected in Hodgkin's disease derived cell lines and in normal hematopoietic cells. Transcripts of the proto-oncogene c-met were detected in the Hodgkin's derived cell lines L428 and L540 but not in the lymphoid or myeloid leukemia cell lines or in tonsil cells, peripheral blood mononuclear cells and granulocytes. Expression of the proto-oncogenes N-myc and lck were observed in the Hodgkin's derived cell line CO which express T cell receptor genes and in the T cell lines JM and CEM. L428 cells and CO cells expressed aberrant transcripts of the c-fes proto-oncogene. Thus Hodgkin's disease derived cell lines are heterogeneous in their expression pattern of proto-oncogenes, expressing normal and aberrant transcripts of proto-oncogenes which are not found in untransformed hematopoietic cells.
 ...
PMID:Heterogeneous expression of proto-oncogenes in Hodgkin's disease derived cell lines. 221 Jun 88

MDM2 and p53 immunohistochemical protein expression was analysed in lymphocytes and in reactive and neoplastic lymphoid tissue. Phytohaemagglutinin (PHA)-stimulated lymphocytes displayed MDM2 and p53 co-expression. In 8 of 8 tonsils, 24 of 24 Hodgkin's disease (HD), and 10 of 24 high-grade non-Hodgkin's lymphoma (HG-NHL) specimens, MDM2 paralleled p53 nuclear expression in non-tumour and tumour cells. The number of positive cells was greater and the staining intensity was stronger for p53 than for MDM2. In another nine of the 24 HG-NHL cases studied, dissociated expression was observed, with high p53 expression and very low or absent MDM2 expression. In five cases, both MDM2 and p53 were negative. The eight low-grade NHL (LG-NHL) cases were also MDM2- and p53-negative. MDM2 and p53 expression in PHA-activated lymphocytes and reactive lymphoid tissue is probably an expression of opposing biological signals regulating cell proliferation. Parallel MDM2 and p53 expression in all HD and in 10 out of 24 HG/NHL cases may indicate that this growth suppressive pathway is maintained in those cases. However, dissociated MDM2/p53 expression (nine cases) and the absence of expression of both proteins (five cases) may represent examples of deregulation of this growth control pathway. These findings are in agreement with previous in vitro studies in cell lines regarding the role of MDM2/p53 lymphoid tissue, suggesting a possible role for MDM2 deregulation in lymphomagenesis.
 ...
PMID:MDM2 expression in lymphoid cells and reactive and neoplastic lymphoid tissue. Comparative study with p53 expression. 747 76


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