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 posttransplantation lymphoproliferative disorders (PT-LPDs) are a morphologically heterogeneous group of Epstein-Barr virus (EBV)-driven lymphoid proliferations of varying clonal composition. Some PT-LPDs regress after a reduction in immunosuppression, while others progress in spite of aggressive therapy. Previously defined morphologic categories do not correlate with clonality, and neither morphology nor clonality has reliably predicted the clinical behavior of PT-LPDs. We investigated 28 PT-LPD lesions occurring in 22 patients for activating alterations involving the bcl-1, bcl-2, c-myc, and H-, K- and N-ras proto-oncogenes and for mutations involving the p53 tumor suppressor gene. We correlated the results of these studies with the morphology of the lesions, their clonality based on Ig heavy and light chain gene rearrangement analysis, and the presence and clonality of EBV infection. We found that the PT-LPDs are divisible into three distinct categories as follows: (1) plasmacytic hyperplasia: most commonly arise in the oropharynx or lymph nodes, are nearly always polyclonal, usually contain multiple EBV infection events or only a minor cell population infected by a single form of EBV, and lack oncogene and tumor suppressor gene alterations; (2) polymorphic B-cell hyperplasia and polymorphic B-cell lymphoma: may arise in lymph nodes or various extranodal sites, are nearly always monoclonal, usually contain a single form of EBV, and lack oncogene and tumor suppressor gene alterations; and (3) immunoblastic lymphoma or multiple myeloma: present with widely disseminated disease, are monoclonal, contain a single form of EBV, and contain alterations of one or more oncogene or tumor suppressor genes (N-ras gene codon 61 point mutation, p53 gene mutation, or c-myc gene rearrangement). The PT-LPDs are divisible into three categories exhibiting distinct morphologic and molecular genetic characteristics. Alterations involving the N-ras and c-myc proto-oncogenes and the p53 tumor suppressor gene may play an important role in the development and/or progression of the PT-LPDs.
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PMID:Correlative morphologic and molecular genetic analysis demonstrates three distinct categories of posttransplantation lymphoproliferative disorders. 781 11

This review addresses several current questions about Hodgkin's disease (HD): 1) Does HD represent a single disease or multiple diseases? 2) What is the role of cytokines in HD? 3) What is the nature of the Reed-Sternberg cell? 4) How are Epstein-Barr virus (EBV) and oncogenes (bcl-2, c-myc, and p53) involved in the pathogenesis of HD? Nodular lymphocyte predominance HD appears to be a distinct clinicopathologic entity. Cytokines attract inflammatory cells, induce fibrosis, upregulate oncogenes and adhesion molecules, cause systemic symptoms, and mediate immune suppression. Reed-Sternberg cells are derived from B and T lymphocytes in most instances, although an alternative origin from a follicular dendritic reticulum cell has been proposed. EBV is an etiologic agent in some but not all HD cases. EBV gene products confer a growth advantage on Reed-Sternberg cells. The bcl-2 and p53 oncogenes protect Reed-Sternberg cells from apoptosis and are not directly upregulated by EBV.
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PMID:Pathology of Hodgkin's disease. 782 47

Lymphoma is one of the defining manifestations of AIDS. Most of these lymphoproliferations are high-grade B-cell non-Hodgkin's lymphoma. Unlike lymphoproliferations that arise in other settings of immunodeficiency, HIV-related lymphomas have a variable association with Epstein-Barr virus (EBV) and also contain alterations in c-myc and p53. EBV infection appears to precede clonal expansion, and its latent expression pattern (Epstein-Barr nuclear antigen1+/Epstein Barr nuclear antigen 2-/latent membrane protein+) is unique among non-Hodgkin's lymphomas. Both EBV types A and B are present in HIV-related lymphomas. Mutations in c-myc include translocations and point mutations. Other altered loci include ras and bcl-6. Although all of these somatic alterations can be detected in lymphomas arising in the general population, their accumulation in a relatively short period (6 to 8 years) after HIV infection suggests an acceleration of underlying mechanisms.
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PMID:Biologic aspects of AIDS-related lymphoma. 782 54

Tumor biopsies obtained from 25 Saudi Arab patients with nasopharyngeal carcinoma (NPC) were examined for the presence of Epstein-Barr virus (EBV) DNA detected by the polymerase chain reaction (PCR) and for the incidence of p53 mutations screened by a combination of PCR, single strand conformation polymorphism (SSCP) and PCR-restriction fragment length polymorphism (PCR-RFLP). DNA sequencing was carried out to confirm the occurrence of p53 mutation. While 92% of the tumor specimens were found to carry EBV DNA, only 1/25 showed the incidence of a homozygous mutation at codon 248 of the p53 gene. The data showed that despite a high association of EBV infection with Saudi NPC, the frequency of p53 mutations was very low. Our results are consistent with the worldwide observation of infrequent p53 mutations in NPC.
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PMID:A molecular study of EBV DNA and p53 mutations in nasopharyngeal carcinoma of Saudi Arab patients. 791 50

We have characterized a new Epstein-Barr-virus(EBV)-like herpesvirus associated with lymphomas of SIV-infected cynomolgus (Macaca fascicularis) monkeys and propose that this virus is designated herpesvirus macaca fascicularis I (HVMFI). Genomic regions in HVMF1 of potential significance for tumor pathogenesis were analyzed by Southern blotting, PCR and sequencing, and compared with human EBV DNA. Virus from 7 SIV-associated lymphomas and one lymphoma-derived cell line were shown to share homology with the EBNA1- and EBNA2-coding regions of EBV, while some homology to EBV-LMP1 was detectable only at low-stringency hybridization. Homologous regions to the long internal repeat (IR1; BamHI W), the EBER1 and 2 and the latent origin of DNA replication (oriP) could also be demonstrated in HVMF1. These coding regions, except IR1, showed restriction-enzyme maps different from those of EBV. Sequencing of the EBNA5 homologous region of HVMF1 DNA, corresponding to exons W1 and W2, showed 65% homology to the EBV exons W1 and W2, and 80% to the whole region including the intron. Since EBNA5 has been reported to bind tumor-suppressor proteins p53 and Rb in vitro, the HVMF1 homology could be important for the lymphomagenic capacity of this monkey herpesvirus.
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PMID:DNA of lymphoma-associated herpesvirus (HVMF1) in SIV-infected monkeys (Macaca fascicularis) shows homologies to EBNA-1, -2 and -5 genes. 792 31

A high frequency of lymphoma in human immunodeficiency virus-infected individuals has been reported since the outbreak of the acquired immunodeficiency syndrome (AIDS) epidemic in 1982. AIDS-associated non-Hodgkin's lymphoma (AIDS-NHL) is almost invariably derived from B cells and is classified as high- or intermediate-grade NHL, according to the working formulation. Two main histologic types are recognized, including small noncleaved cell lymphoma (SNCCL) and diffuse large cell lymphoma (DLCL). Pre-existing host factors putatively involved in lymphoma development include disrupted immunosurveillance, deregulated cytokine production, chronic antigen stimulation, and infection by Epstein-Barr virus (EBV). These alterations are associated with the development of multiple oligoclonal expansions which correspond to the clinical phase known as persistent generalized lymphadenopathy (PGL). The appearance of a true AIDS-NHL is characterized by the presence of a monoclonal B-cell population displaying several genetic lesions, including monoclonal EBV infection, c-MYC and BCL-6 rearrangements, RAS mutations, p53 inactivation, and 6q deletions. These genetic lesions cluster into two distinct molecular pathways, which specifically associate with the different histologic subtypes of AIDS-NHL, i.e., AIDS-SNCCL and AIDS-DLCL. The presence of distinct genetic pathways for AIDS-SNCCL and AIDS-DLCL correlate with a number of clinical features which distinguish these two groups of tumors, including differences in the age of onset, CD4 counts at the time of presentation, time elapsed since HIV infection, and clinical outcome.
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PMID:Molecular pathology of AIDS-related lymphomas. Biologic aspects and clinicopathologic heterogeneity. 799 35

Lymphoepithelial carcinoma (Schmincke's tumor) is a relatively common malignancy in the upper respiratory tract (nasopharynx), but it rarely occurs at other sites. We describe here the first case of a vaginal neoplasm that closely resembled lymphoepithelial carcinoma in its histological features and immunophenotype. The tumor was detected in an 81-year-old woman who presented with recurrent vaginal bleeding. On colposcopy, an ulcerated polypoid tumor mass was seen in the posterior wall of the middle portion of the vagina. Histologic examination revealed an undifferentiated spindle-cell carcinoma (KL1+, chromogranin A-, vimentin-) with abundant lymphocytes (mostly UCHL1+ T cells), plasma cells, and macrophages (CD68+) in and around the tumor cell nests. A minority of the tumor cells exhibited overexpression of p53 protein and a quarter of the tumor cells reacted with the antibody MIB1, that is, were in a proliferate state. The tumor cells did not react with the monoclonal antibody DAKO-EBV, which detects a latent membrane protein (LMP-1) encoded by the Epstein-Barr virus. The tumor underwent regression after radiotherapy. No signs of recurrence or dissemination of the carcinoma have been detected clinically during the 6 months since treatment.
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PMID:Lymphoepithelioma-like carcinoma of the vagina: a case report with special reference to the immunophenotype of the tumor cells and tumor-infiltrating lymphoreticular cells. 800 41

Acquired immunodeficiency syndrome (AIDS)-associated non-Hodgkin's lymphomas (AIDS-NHL), a major source of morbidity and mortality among AIDS patients, are derived from B cells and can be classified into two main histologic categories, small noncleaved cell lymphoma (SNCCL) and diffuse large-cell lymphoma (DLCL). DLCL includes two histologic subsets, ie, large noncleaved cell lymphoma (LNCCL) and large cell-immunoblastic plasmacytoid lymphoma (LC-IBPL). Several studies have shown that AIDS-SNCCL is associated with the clonal accumulation of multiple genetic lesions, including Epstein-Barr virus (EBV) infection, activation of the c-MYC and RAS oncogenes, as well as inactivation of the p53 tumor suppressor gene at variable frequencies. On the contrary, the molecular pathogenesis of AIDS-DLCL is largely obscure, because no genetic lesion other than EBV infection has been specifically identified in this group. In this study, we have tested a panel of 40 AIDS-NHL for structural alterations of BCL-6, a putative proto-oncogene that is frequently altered in DLCL in the immunocompetent host. Our results show that rearrangements of BCL-6 are present in 20% of AIDS-DLCL (5 of 24), including 2 of 8 LNCCL and 3 of 16 LC-IBPL, but in no case of AIDS-SNCCL. BCL-6 rearrangements were detected both in the presence and in the absence of EBV infection of the tumor clone, but in no case were associated with activation of c-MYC or mutations of p53. These data identify a novel genetic lesion in AIDS-DLCL and corroborate the notion that lymphomagenesis in AIDS follows two distinct molecular pathways that are associated with the development of histologically distinct types of AIDS-NHL.
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PMID:Rearrangements of the BCL-6 gene in acquired immunodeficiency syndrome-associated non-Hodgkin's lymphoma: association with diffuse large-cell subtype. 802 68

Small DNA viruses are dependent on the interaction of early proteins (such as large T antigen) with host p53 and Rb to bring about the G1-to-S cell cycle transition. The large DNA viruses are less dependent on host regulatory genes since additional early viral proteins (such as viral DNA polymerase, DNA metabolic enzymes, and other replication proteins) are involved in DNA synthesis. A highly conserved domain of large T antigen (similar to the p53-binding region) exclusively identifies papovavirus, parvovirus, and papillomaviruses from all other larger DNA viruses and implies a conserved interaction with host regulatory genes. In this report, we show that 3 to 6 mM butyrate, a general cell cycle blocker implicated in inhibition of the G1-to-S transition, inhibits DNA replication of polyomavirus and human papillomavirus type 11 but not the replication of larger DNA viruses such as adenovirus types 2 and 5, herpes simplex virus type 1, Epstein-Barr virus, and cytomegalovirus, which all bypass the butyrate-mediated cell cycle block. This butyrate effect on polyomavirus replication is not cell type specific, nor does it depend on the p53 or Rb gene, as inhibition was seen in fibroblasts with intact or homozygous deleted p53 or Rb, 3T6 cells, keratinocytes, C2C12 myoblasts, and 3T3-L1 adipocytes. In addition, butyrate did not inhibit expression of polyomavirus T antigen. The antiviral effect of butyrate involves a form of imprinted state, since pretreatment of cells with 3 mM butyrate inhibits human papillomavirus type 11 DNA replication for at least 96 h after its removal. Butyrate, therefore, serves as a molecular tool in dissecting the life cycle of smaller DNA viruses from that of the larger DNA viruses in relation to the cell cycle.
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PMID:n-Butyrate, a cell cycle blocker, inhibits the replication of polyomaviruses and papillomaviruses but not that of adenoviruses and herpesviruses. 803 79

Biopsies from 34 patients with cancer of the head, neck or esophagus, 2 laryngeal papillomas, and 2 normal tonsils were analysed for human papillomavirus (HPV), Epstein Barr virus (EBV) genomes and mutated or elevated levels of p53. In 4 biopsies p53 was also analysed by DNA sequencing. HPV type 31 was found in one laryngeal cancer with normal p53 and HPV type 16 in two tonsil cancers with aberrant p53 expression. EBV was detected by PCR in 11 biopsies, but in situ hybridisation and immunohistochemistry, did not confirm this finding. Aberrant p53 expression was observed in approximately half of the tumours. These results support the involvement of both aberrant p53 expression and HPV in the aetiology of squamous cell carcinoma of the head and neck.
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PMID:Involvement of aberrant p53 expression and human papillomavirus in carcinoma of the head, neck and esophagus. 806 97


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