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)

Contact-inhibited Kaposi's sarcoma-derived cells (KS cells) were transfected with Simian Virus 40 (SV40) DNA. Transformed cells (SV-KSC) were selected for their capacity to form foci on monolayers of the low-malignant KS cells. Isolated SV-KSC foci were found to contain integrated SV40 DNA sequences and to express SV40 large T-antigen. Several differentiation properties of KS cells are retained in the SV40 transformants, e.g., expression of vimentin and the endothelial cell marker BMA 120. In contrast to the maternal KS cells, SV-KSC are capable of growing in platelet-derived growth factor (PDGF)-depleted platelet-poor-plasma serum (PPPS) and in soft agar. However, they are not tumorigenic in nude mice. Expression of the oncogenes c-myc, c-N-ras, c-Ha-ras, and p53 is significantly elevated in SV-KSC, whereas c-fos and c-erb B expression is comparable to that of KS cells and fibroblasts. Conditioned medium from SV-KSC can substitute for PDGF when PDGF-dependent, nontransformed KS cells are grown in PPPS. Biochemical analysis of the SV-KSC supernatant and PDGF A and B mRNA expression analysis provide evidence that the mitogenic activity is not due to a PDGF-like growth factor. On the other hand, there is evidence to indicate that the SV-KSC mitogen is a member of the fibroblast growth factor family. SV-KSC represent an interesting model system for the study of different degrees of malignancy of cultured mesenchymal cells and especially provide an important source for the isolation of a potent growth factor for KS cells and other mesenchymal cells in vitro.
 ...
PMID:Cytochemical and molecular properties of simian virus 40 transformed Kaposi's sarcoma-derived cells: evidence for the secretion of a member of the fibroblast growth factor family. 255 9

Epidemiological evidence indicates that a sexually transmitted agent might be involved in the etiopathogenesis of Kaposi's sarcoma (KS). The prevalence of human papillomaviruses (HPV) in KS has been the focus of several investigations that have reported conflicting data. In addition, mutations of the p53 gene, which are the most frequent genetic changes found in human tumors, are absent in HPV-positive cervical carcinomas leading to the hypothesis that the function of p53 in HPV-positive tumors is inactivated through binding to the E6 viral gene product. Thus, the present study was designed to investigate the presence of HPV and p53 gene mutations in 17 formalin-fixed, paraffin-embedded KS [7 acquired immunodeficiency syndrome-KS (AIDS-KS) and 10 classic KS] specimens. HPV 6 DNA was detected in an AIDS-KS specimen, and HPV 16 DNA was found in 3 classic KS specimens. Heterozygous mutations of the p53 gene were detected in five (24%) KS samples. No p53 mutations were detected in HPV-positive KS. The p53 mutations were mainly transversions (four of five). These data indicate that HPV may contribute to the pathogenesis of some cases of KS and that p53 alteration may represent a key event in the progression of the malignancy.
 ...
PMID:Occurrence of human papillomavirus and p53 gene mutations in Kaposi's sarcoma. 803 Feb 71

AIDS-related non-Hodgkin's lymphomas (AIDS-NHLs) are almost invariably derived from B cells and are grouped into three distinct histologic categories, including small-non-cleaved-cell lymphoma (SNCCL), diffuse large-cell lymphoma (DLCL), and anaplastic large-cell lymphoma (ALCL). In addition, AIDS-NHLs presenting solely as a body cavity effusion are thought to be a peculiar clinicopathologic entity and are defined as body-cavity-based lymphoma (BCBL). At the biologic level, AIDS-related lymphomagenesis is characterized by activation of proto-oncogenes, inactivation of tumor suppressor genes, viral infection of the tumor clone, and deregulated cytokine production. Distinct AIDS-NHL types associate with specific molecular pathways. The first pathogenetic pathway clusters with AIDS-SNCCL, and is characterized by a relatively mild degree of host immunodeficiency. AIDS-SNCCL consistently associates with c-myc rearrangements and p53 inactivation in 100 and 60% of cases, respectively, whereas infection by Epstein-Barr virus (EBV) is restricted to 30% of the cases. Production of high levels of interleukin-10 is an additional peculiar feature of EBV-positive AIDS-SNCCL. The second pathogenetic pathway associates with AIDS-DLCL, which is usually accompanied by marked host immunodeficiency. AIDS-DLCL is characterized by EBV infection in the large majority of cases and by the mutually exclusive presence of bcl-6 rearrangements and c-myc translocations in 40% of the cases. A third pathway characterizes AIDS-BCBL, which associates in virtually all cases with infection by EBV and with the presence of DNA sequences of the recently identified Kaposi sarcoma herpesvirus in the apparent absence of other known genetic lesions. Finally, the pathogenetic features of AIDS-ALCL are still under investigation.
 ...
PMID:AIDS-related non-Hodgkin's lymphomas: molecular genetics, viral infection and cytokine deregulation. 867 42

We recently discovered the Kaposi's sarcoma-associated herpes virus (KSHV/HHV-8) in an uncommon and unusual subset of AIDS-related lymphomas that grow mainly in the body cavities as lymphomatous effusions without an identifiable contiguous tumor mass. The consistent presence of KSHV and certain other distinctive features of these body cavity-based lymphomas suggest that they represent a distinct entity. We tested this hypothesis by investigating 19 malignant lymphomatous effusions occurring in the absence of a contiguous tumor mass for their clinical, morphologic, immunophenotypic, viral, and molecular characteristics, KSHV was present in 15 of 19 lymphomas. All four KSHV-negative lymphomatous effusions exhibited Burkitt or Burkitt-like morphology and c-myc gene rearrangements and, therefore, appeared to be Burkitt-type lymphomas occurring in the body cavities. In contrast, all 15 KSHV-positive lymphomatous effusions exhibited a distinctive morphology bridging large-cell immunoblastic lymphoma and anaplastic large-cell lymphoma, and all 12 cases studied lacked c-myc gene rearrangements. In addition, these lymphomas occurred in men (15/15), frequently but not exclusively in association with HIV infection (13/15), in which homosexuality was a risk factor (13/13), presented initially as a lymphomatous effusion (14/15), remained localized to the body cavity of origin (13/15), expressed CD45 (15/15) and one or more activation-associated antigens (9/10) in the frequent absence of B-cell-associated antigens (11/15), exhibited clonal immunoglobulin gene rearrangements (13/13), contained Epstein-Barr virus (14/15), and lacked bcl-2, bcl-6, ras and p53 gene alterations (13/15). These findings strongly suggest that the KSHV-positive malignant lymphomatous effusions represent a distinct clinicopathologic and biologic entity and should be distinguished from other malignant lymphomas occurring in the body cavities. Therefore, we recommend that these malignant lymphomas be designated primary effusion lymphomas (PEL), rather than body cavity-based lymphomas, since this term describes them more accurately and avoids their confusion with other malignant lymphomas that occur in the body cavities. We further recommend that these PEL be considered for inclusion as a new entity in the Revised European-American Lymphoma Classification.
 ...
PMID:Primary effusion lymphoma: a distinct clinicopathologic entity associated with the Kaposi's sarcoma-associated herpes virus. 869 12

The aim of this study was to examine the immunohistochemical expression of p53 and bcl-2 in Kaposi's sarcoma and relate this with proliferation index (as measured by MIB-1 staining) and clinicopathological subtypes. Twenty formalin-fixed, paraffin-embedded cases of Kaposi's sarcoma were stained with commercially available antibodies to p53, bcl-2 and MIB-1, after pressure cooking antigen retrieval. All cases were strongly positive for bcl-2 with the majority containing more than 75% positive cells. In comparison, p53 expression was less striking. Eleven cases contained less than 24% (+1) of cells staining positively. Only two cases showed greater than 75% of positive cells, and both of these latter two lesions had metastasized. The MIB-1 staining in all cases of Kaposi's sarcoma was strongly positive, irrespective of clinicopathological type, in keeping with the highly proliferative nature of this lesion. Thus, we have demonstrated uniformly increased expression of bcl-2 protein in Kaposi's sarcoma irrespective of clinicopathological subtype and MIB-1 staining, while p53 expression is relatively less common, except in those cases which have metastasized. This may help identify those cases that will behave in a more aggressive manner. However, more cases need to be evaluated to verify this.
 ...
PMID:The immunoexpression of bcl-2 and p53 in Kaposi's sarcoma. 887 50

The present study was performed to determine the frequency of p53 protein immunoreactivity in classical Kaposi's sarcoma (KS) as a whole and in relation to the histological subtypes which are considered to correspond to the developmental stages of the tumor. The accumulation of p53 protein was studied immunohistochemically using monoclonal antibody BP53-12 on formalin-fixed paraffin-embedded sections of 36 KS lesions, of which 14 were classified histologically as early type and 22 as spindle-cell or mixed type. No positive immunoreactivity was detected in any of the 14 early-type lesions. Among the 22 spindle-cell and mixed variants, positive staining was detected in 5-10% of the tumor cells in one lesion, 1-5% of the cells in six lesions, and in < 1% of the cells in two lesions. These very small percentages of positively stained cells in less than half of the cases of the spindle-cell and mixed variants do not support a significant role for p53 in tumor progression and evolution in KS.
 ...
PMID:An immunohistochemical study of p53 protein expression in classical Kaposi's sarcoma. 941 25

In 1987, we reported three patients with pleural lymphoma developed after a 22-30 year history of pyothorax resulting from artificial pneumothorax for the treatment of pulmonary tuberculosis or tuberculous pleuritis. Based on the pathologic and epidemiologic studies, we regarded the chronic pyothorax (CP) to be etiologically important in the development of pleural lymphoma. Through a nation-wide study in Japan, 37 cases of pleural lymphoma were collected. Pleural lymphoma had developed during the 20 year history of CP in all patients. Histologically all were non-Hodgkin's lymphoma with the diffuse large cell type being the most common. Immunologic and immunohistochemical studies revealed that 32 out of 33 cases were of B-cell lymphoma. From these findings, we proposed the term pyothorax-associated lymphoma (PAL). We examined the presence of Epstein-Barr virus (EBV) genome on the paraffin-embedded specimens in 34 PAL cases and 16 cases of CP alone. Combined polymerase chain reaction (PCR), in situ hybridization, and immunohistochemistry revealed that the EBV genome was detected in lymphoma cells in all PAL, but only one of the cases with CP alone. These findings suggested the etiological role of EBV for the development of PAL. We also described here the character of cell lines established from PAL, association of PAL with Kaposi's sarcoma-associated herpes virus, results of a case-control study on risk factors for development of PAL, and p53 mutations.
 ...
PMID:Pyothorax-associated lymphoma. 899 Jun 21

The incidence of non-Hodgkin's lymphoma is greatly increased in human immunodeficiency virus (HIV)-infected individuals. Most are clinically aggressive B-cell lymphomas exhibiting Burkitt-type, immunoblastic or large-cell morphology. Approximately 80% arise systemically (nodal or extranodal), and the remaining 20% arise in the central nervous system. A small proportion are body cavity-based (primary effusion) lymphomas associated with Kaposi's sarcoma-associated herpesvirus (KSHV) infection. Possible factors contributing to lymphoma development include HIV-induced immunosuppression, chronic antigenic stimulation, and cytokine overproduction. These phenomena are associated with the development of oligoclonal B-cell expansions. The appearance of malignant lymphoma is characterized by the presence of a monoclonal B-cell population displaying a variety of genetic lesions including Epstein-Barr virus (EBV) infections, c-myc gene rearrangement, bcl-6 gene rearrangement, ras gene mutations, and p53 gene mutations/deletions. The number and type of genetic lesions varies according to anatomic site of origin and histopathology. In the case of Burkitt-type lymphoma, virtually 100% exhibit c-myc gene rearrangement, two thirds display p53 gene mutations, one third contain EBV, and none exhibit bcl-6 gene rearrangements. In contrast, in the case of immunoblastic lymphoma, virtually 100% contain EBV, 25% display c-myc gene rearrangements, 20% display bcl-6 gene rearrangements, and few exhibit p53 gene mutations. These findings suggest that more than one pathogenetic mechanism is operational in the development and progression of acquired immunodeficiency syndrome (AIDS)-related lymphoma. Further work is necessary to develop a thorough understanding of the origin and pathogenesis of malignant lymphoma in the setting of HIV infection. AIDS-related lymphoma remains an important biologic model for investigating the development and progression of high-grade non-Hodgkin lymphomas as well as malignant lymphomas that develop in immune-deficient hosts.
 ...
PMID:Molecular pathology of acquired immunodeficiency syndrome-related non-Hodgkin's lymphoma. 904 11

Primary plasmacytoma of the lymph nodes is very rare, and there are fewer than 20 reported cases. These cases appeared to have a better prognosis than other extramedullary plasmacytomas, with rare recurrence and no progression to myeloma after treatment. To better characterize the clinicopathological features and the pathogenesis of primary plasmacytoma of the lymph nodes, we reviewed our consultation files and retrieved seven such cases. The age of presentation ranged from 39 to 76 years (median age, 59 years), with three women and four men. The clinical follow-up varied from 1 to 14 years. All patients presented with enlarged lymph nodes and had an indolent clinical course, except for one patient with slow progression and increasing numbers of bone marrow plasma cells. Five patients were treated with excision only and two with excision and chemotherapy. None of the patients had recurrence or developed multiple myeloma. All cases showed immunoglobulin light chain restriction, four with monotypic lambda and three with monotypic kappa. One patient had extensive nodal amyloid deposition. Four cases had monoclonal heavy chain expression, three with monoclonal immunoglobulin (Ig) G and one with monoclonal IgM. All cases were negative for CD20 and CD43, and six cases expressed CD79a. Overexpression of p53 and bcl-2 was not detected by immunostaining in any of the cases. Epstein-Barr viral (EBV) RNA was not detected in all seven cases by in situ hybridization, and no Kaposi's sarcoma-associated herpesvirus (KSHV) DNA sequences were detected by polymerase chain reaction in five cases. Our results confirm a more favorable outcome and rare progression to multiple myeloma in primary nodal plasmacytomas after excision or chemotherapy. The results of oncoprotein and viral studies suggest that the pathogenesis of primary nodal plasmacytoma may not be due to bcl-2- and p53-associated changes or viral-induced changes by EBV and KSHV.
 ...
PMID:Primary plasmacytoma of lymph nodes. 930 34

Twenty-seven lymphomas of mucosa-associated lymphoid tissue (MALT) derived from distinct anatomical sites were tested for the presence of genetic lesions commonly involved in B-cell lymphomagenesis, including activation of proto-oncogenes (BCL-1, BCL-2, BCL-6, and c-MYC), disruption of tumor suppressor loci (p53, 6q), and infection by viruses [Epstein-Barr virus (EBV), and Kaposi's sarcoma-herpesvirus/human herpesvirus-8 (KSHV/HHV-8)]. Sixteen low-grade and 11 high-grade MALT-lymphomas were included in the study. The presence of genetic lesions was tested by a combination of molecular approaches, including Southern blot hybridization, polymerase chain reaction (PCR), and PCR-single strand conformation polymorphism followed by DNA direct sequencing. Alterations of BCL-1, BCL-2, or c-MYC, as well as infection by KSHV/HHV-8, scored negative in all MALT-lymphomas analysed. Conversely, rearrangements of BCL-6 and mutations of p53 clustered with a fraction of high-grade MALT-lymphomas. Deletions of 6q occurred in selected cases of both low- and high-grade MALT-lymphomas, whereas a monoclonal infection by EBV was restricted to one single patient. These data corroborate the notion that the molecular pathogenesis of MALT-lymphomas differs substantially from that of nodal B-cell lymphomas. Occasionally, however, a proportion of high-grade MALT-lymphomas may harbor selected genetic lesions among the ones commonly involved in nodal B-cell lymphomagenesis.
 ...
PMID:Detection of BCL-6 rearrangements and p53 mutations in Malt-lymphomas. 939 80


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