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

The authors analyzed the possible occurrence of rearrangements and/or allelic loss of the fas/APO-1 gene in a representative series of human lymphomas, including 101 cases of Hodgkin's disease (HD) and non-Hodgkin's lymphomas (NHL). The rationale for this study was double. Chromosome 10 alterations, frequently observed in lymphoma subtypes, encompass the chromosomal localization of fas/APO-1. In addition, Ipr mouse mutants, which present with a generalized lymphoproliferative disease, were shown to exhibit alterations of fas/APO-1 structure and expression. In this retrospective study, the authors performed gene dosage of fas/APO-1 by Southern blots. No fas/APO-1 alterations were observed in the 31 HD cases. Among 70 T-cell and B-cell NHL, allelic loss of fas/APO-1 was observed in three cases. Two cases with different clinical, phenotypic, and histologic presentations showed a rearrangement of fas/APO-1. A third case showed amplification. Thus fas/APO-1 alterations do occur in human lymphomas, although at a relatively low frequency.
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PMID:Search for rearrangements and/or allelic loss of the fas/APO-1 gene in 101 human lymphomas. 757 93

The relationship between the number of apoptotic cells and the expression of apoptosis-related antigens was examined in 56 cases of non-Hodgkin's lymphomas and in 10 cases of reactive hyperplastic lymph nodes (RHL). Apoptosis was visually quantified by the in situ end-labeling (ISEL) method, and the expression of Fas, Le(y) antigens and bcl-2 protein was examined by immunohistochemistry. The expression of Le(y) antigen was observed in germinal centers of RHL and 45% of non-Hodgkin's lymphomas. The apoptotic cell count (AC) in follicular lymphomas was significantly less than that in diffuse lymphomas. The distribution pattern of apoptotic cells in follicular lymphomas was inverse to that in RHL. In follicular lymphomas, AC was lower in follicles than in interfollicular areas. In contrast, AC was higher in follicles than in interfollicular areas in RHL. Le(y) antigen-positive lymphomas showed a significantly higher AC than the negative cases. The Fas antigen-positive lymphomas showed a higher AC than the negative cases. However, AC in bcl-2 protein-positive and negative cases was not significantly different. These results suggest that Ley and Fas antigens appear to be involved in the apoptotic tendency of tumor cells in non-Hodgkin's lymphomas, whereas bcl-2 does not necessarily.
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PMID:Correlation between the number of apoptotic cells and expression of the apoptosis-related antigens Fas, Le(y) and bcl-2 protein in non-Hodgkin's lymphomas. 758 33

FAS/APO-1 (CD95) is a membrane glycoprotein belonging to the tumour necrosis factor/nerve growth factor receptor family, and which can trigger apoptosis in some lymphoid cell lines. Immunohistochemistry combined with Northern blotting allowed determination of the pattern of FAS/APO-1 expression in a series of Ki-1 [CD30] positive lymphoid malignancies, including 27 Hodgkin's disease and eight anaplastic large cell lymphomas. CD30 negative tumours used as controls included 27 B-cell non-Hodgkin's lymphomas. 14 T-cell non-Hodgkin's lymphomas, four reactive lymphadenitis, and non-lymphoid tissues. Immunohistochemistry, performed on frozen sections, revealed a strong FAS/APO-1 expression in 25 out of 27 (92%) Hodgkin's disease cases, predominantly in Reed Sternberg cells; 50 to 100% of the neoplastic cells in eight out of (100%) anaplastic large cell lymphoma cases were positive. In contrast, positive FAS/APO-1 immunostaining was observed only in 22 out of 41 (53%) CD30 negative non-Hodgkin's lymphomas. Northern blot analysis detected variable amounts of the FAS/APO-1 transcript in the immunohistochemistry-positive samples. These results suggest possible hyper-expression of FAS/APO-1 (CD95) in Hodgkin's disease and anaplastic large cell lymphomas.
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PMID:Frequent expression of FAS/APO-1 in Hodgkin's disease and anaplastic large cell lymphomas. 852 87

We determined Fas antigen (CD95) expressions on neoplastic cells from various lymphoid malignancies including adult T-cell leukemia/lymphoma (ATL/L) by a flow cytometoric method. ATL/L cells generally expressed Fas antigen, while few Fas-positive cells were detected in the other lymphoid malignancies such as non-Hodgkin lymphomas, acute lymphoblastic leukemias, and chronic lymphocytic leukemias. The function of Fas antigen was considered normal, since anti-Fas monoclonal antibody induced apoptosis of ATL/L cells. However, clinical subtypes of ATL/L did not associate with the degrees of Fas antigen expression. When recent observations by others were also considered, the apoptosis of ATL/L cells seemed to be under a complex control mechanism which includes a Fas/Fas-ligand system, HTLV-I Tax protein, bcl-2 protein and interleukin-2 (IL-2)/IL-2 receptor system. In addition, the regulation of apoptosis by Fas/Fas-ligand system and bcl-2 protein might be different between T-and B-lineage lymphoid malignancies.
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PMID:[Fas antigen (CD95) expressions and apoptosis of neoplastic cells from various lymphoid malignancies including adult T-cell leukemia/lymphoma]. 874

CD95 (APO-1/Fas) is a member of the superfamily that includes the nerve growth factor and tumor necrosis factor receptors, OX40, CD27, CD30, and CD40. Present on a minority of resting blood lymphocytes, CD95 expression is upregulated on activated T and B lymphocytes and natural killer cells, where binding of the antigen by anti-Fas and anti-APO-1 antibodies has been shown to induce apoptosis. This CD95-mediated apoptosis is at least partially inhibited by expression of the Bcl-2 protooncogene. To evaluate possible roles of CD95 and Bcl-2 in growth regulation of lymphoid neoplasms, we studied by immunohistochemistry the expression of CD95 and Bcl-2 in 67 B- and 5 T-cell lymphomas, and 10 cases of Hodgkin's disease. In all, 29 B and 2 T cell lymphomas, and 9 cases of Hodgkin's disease expressed CD95. Compared with diffuse large B-cell and Burkitt-like lymphomas, lowgrade B-cell lymphomas more frequently expressed CD95 (52% versus 26%; P < .005). None of the B-cell small lymphocytic lymphomas or mantle cell lymphomas expressed CD95, whereas the majority of follicle center lymphomas, extranodal marginal zone B-cell lymphomas, and immunocytomas were CD95+. Of the 29 CD95+ B-cell lymphomas, only 33% of the high-grade group coexpressed Bcl-2, compared with 87% of the low-grade group (P < .04). Two of three peripheral T-cell lymphomas--including one anaplastic large cell lymphoma--expressed CD95. Staining for CD95 was seen in 9 of 10 cases of Hodgkin's disease. The infrequent expression of CD95 in high-grade B-cell lymphomas suggests an association between loss of CD95 expression/function and a more aggressive tumor grade. Whereas frequent coexpression of Bcl-2 with CD95 may protect low-grade B-cell lymphomas against CD95-mediated apoptosis, in the high-grade group such coexpression is infrequent, and other regulators besides Bcl-2 may be involved in modulating the apoptosis signal delivered by CD95.
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PMID:Expression of CD95 antigen and Bcl-2 protein in non-Hodgkin's lymphomas and Hodgkin's disease. 877 39

Cross-linkage of the CD95 (FAS/APO-1) antigen is responsible for the induction of programmed cell death or apoptosis in a variety of normal and malignant cells of the haemopoietic system. In order to evaluate predominant expression of the CD95 gene in a cell lineage-specific manner, we have determined the CD95 expression patterns in cell lines of myeloid, T-, pre-B- or B-cell origin as well as those established from Hodgkin's disease (HD). Our results reveal constitutive transcriptional activation of the CD95 gene in all cell lines derived from the lymphoid and myeloid lineages. Despite the ubiquitous expression of CD95 transcripts in haemopoietic cells, the corresponding protein was undetectable in 2/5 cell lines derived from Burkitt lymphomas and 6/16 leukaemia cell lines of the megakaryocytic or monocytic lineage. In an effort to identify apoptosis-resistant cell lines resulting from mutations in the death-signalling domain of CD9 5 or from defects in the apoptotic pathway or in survival programmes, we applied a CD95-mediated apoptosis assay. However, 21/38 CD95-expressing cell lines were sensitive upon induction with an anti-CD95 antibody whereas the remaining cell lines (predominantly of myeloid derivation) were resistant to antibody-induced cell death. Resistance to CD95-mediated apoptosis was not due to mutations within the CD95 open reading frame as confirmed by a combined reverse transcription PCR sequencing method. Five myeloid out of 13 tumour lines with the apoptosis-resistance phenotype analysed showed programmed cell death, when protein synthesis was blocked by treatment with cycloheximide prior to CD95-mediated induction. These data suggest an active cellular mechanism for the maintenance of an apoptosis-resistant phenotype. Elucidating the steps in such an active process of resistance to apoptosis might be expected to provide new approaches for therapeutic intervention in certain tumours.
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PMID:Expression and function of CD95 (FAS/APO-1) in leukaemia-lymphoma tumour lines. 905 67

Bispecific monoclonal antibodies (bi-mAb), directed against a tumor-associated antigen and the CD3 or CD28 antigen on T lymphocytes, induce activation of resting T lymphocytes and target-specific tumor cell lysis. We now show that both necrosis and apoptosis contribute to T-cell-mediated tumor cell destruction. Even though T cells up-regulate FAS/APO-1 expression upon bi-mAb stimulation, FAS/APO-1-mediated apoptosis does not contribute to bi-mAb-mediated destruction of Hodgkin's cells. CD8+ lymphocytes were the most potent effectors of bi-mAb-mediated cytotoxicity and had the highest levels of mRNA coding for perforin and granzyme A and B. Ca2+-complexing agents, which abrogate perforin activity, led to decreased levels of necrosis, while inhibition of granzyme activity in effector or target cells had a similar effect on apoptosis. Granzyme-mediated apoptosis critically dependent on the proliferative state of the target cells, while perforin-induced necrosis was not cell-cycle-dependent. Our results underline the importance of the expression levels of perforin and granzymes in the effector T cells and of the proliferative state of the target cells in bi-mAb-mediated apoptosis and necrosis of tumor cells.
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PMID:Role of perforin, granzymes and the proliferative state of the target cells in apoptosis and necrosis mediated by bispecific-antibody-activated cytotoxic T cells. 917 67

The Fas receptor (APO-1/CD95) is capable of inducing apoptosis of lymphoid cells and is expressed in some non-Hodgkin's lymphomas (NHLs). Fas expression is up-regulated at the surface of normal B cells upon triggering of the CD40 receptor. In this report, we investigated the sensitivity of NHLs to Fas-mediated apoptosis induced by anti-Fas monoclonal antibodies (MAbs) and its possible modulation by CD40 ligation in 18 NHL biopsy samples of various histological subtypes. Flow cytometric analysis showed that the fraction of Fas-expressing lymphoma cells was highly variable from sample to sample (from 1% to 93%, mean value 46%). The frequency of apoptotic cells was not significantly increased upon treatment with an anti-Fas MAb compared with control MAb in the 18 NHL cases analysed. The sensitivity of lymphoma cells to Fas-mediated apoptosis was correlated neither with the histological subtypes nor with the level of Fas expression. Activation of neoplastic B cells by CD40 ligation resulted in significant increases in Fas expression and Fas-induced apoptosis among the five B-NHL cases tested. The overall increase in apoptotic rates was moderate and remained lower in tumour samples than in control CD40-activated normal tonsil B cells. Altogether, our results indicate that the sensitivity to Fas-induced apoptosis is null or weak in NHL cells, irrespective of their histological subtype, and that it can be increased to a moderate and variable degree by CD40 ligation on neoplastic B cells. This may be an impediment to the development of Fas-based therapies for NHLs.
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PMID:Sensitivity to Fas-mediated apoptosis is null or weak in B-cell non-Hodgkin's lymphomas and is moderately increased by CD40 ligation. 968 98

CD95 (APO-1/Fas)-mediated apoptosis plays a major role in normal lymphocyte regulation. CD95 mutations cause a benign autoimmune lymphoproliferation syndrome (ALPS) in mice and humans. CD95 is mutated in some de novo T-lineage acute lymphoblastic leukemia of childhood and these mutations might be of biological significance. The resistance toward CD95-mediated apoptosis observed in most B-lineage ALL is not caused by mutations of CD95. CD95 mutations have been associated with Hodgkin's and Non-Hodgkin's lymphoma and have been described in multiple myeloma. The relevance of CD95 mutations for chemoresistance of ALL requires further study.
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PMID:[The role of CD95 (APO-1/Fas) mutations in lymphoproliferative and malignant lymphatic diseases]. 974 45

Apoptosis is a physiological process wherein the cell initiates a sequence of events culminating in the fragmentation of its DNA, nuclear collapse, and finally disintegration of the cell into small, membrane-bound apoptotic bodies. Expression of Fas (APO-1, CD95) Receptor (FasR) and programmed or active cell (PCD) death was studied in childhood astrocytomas (ASTRs) with varying stages of malignancy, including pilocytic ASTR, low grade ASTR, anaplastic ASTR, and glioblastoma multiforme (GBM). The great majority of childhood glial tumors, particularly ASTRs express FasR whereas normal cells in the central nervous system (CNS) do not. FasR represents a transmembrane glycoprotein which belongs to the nerve growth factor/tumor necrosis factor (NGF/TNF) receptor superfamily. Apoptosis within ASTRs is triggered by the binding of FasR to its natural ligand (FasL) or by cross-linking with antibodies developed against FasR. Presence of FasL was also detected in childhood glial tumors. The expression of both FasR and FasL was also observed within the same ASTRs. Therefore, spontaneous, IP regulatory, intratumoral apoptotic cell death (autocrine suicide) is possible in childhood glial tumors. During a systematic, immunocytochemical screening of 42 childhood ASTRs tissues divided according to WHO classification: 6 WHO grade I or pilocytic ASTRs; 14 WHO grade II or low grade ASTRs; 16 WHO grade III or anaplastic ASTRs and 6 WHO grade IV or glioblastoma multiforme (GBM), we detected strong expression (intensity of staining: "A"--the highest possible; number of stained cells: +2 to +4, between 20% to 90%) of FasR, employing 4 microns thick, formalin fixed, paraffin-wax embedded tissue slides. FasR was present on 70% to 90% of tumor cells in pilocytic ASTRs, in 50% to 60% of the tumor cells in low grade ASTRs, in between 30% and 40% of the tumor cells in anaplastic ASTRs, and in between 20% to 35% of GBM cells. The panel of normal tissues employed as positive and negative tissue controls demonstrated presence of FasR in the prenatal thymus, mature tonsils and colonic epithelium. The use of a sensitive, indirect, six step immunoperoxidase or alkaline phosphatase conjugated streptavidin-biotin antigen detection technique provided excellent immunocytochemical results. A broad spectrum of neoplastic cells have been identified to express FasR: 1) carcinomas of epithelial origin, such as breast (ductal invasive, lobular invasive, mucinous), renal cell, gastric, colorectal, endometrial, prostate, pancreas, hepatocellular and large cell and squamous cell lung carcinomas: 2) non-epithelial neoplasms such as B cell mediastinal B cell and nodal non-Hodgkin's lymphomas large granular lymphocytic leukemia of T or NK cell origin malignant fibrous histiocytoma, malignant mesothelioma, leiomyosarcoma, epitheloid sarcoma and alveolar soft part sarcoma, as well as melanomas. Flow cytometry studies have also detected FasR expression on cells of adult T cell, and hairy cell leukemias, as well as in chronic B cell lymphocytic leukemia (BCLL). The coexpression of both FasR and FasL on several malignant cell types may represent an effective mechanism of tumor escape from the cellular immunological response of the host. It has been well established that brain tumors and melanomas produce their autocrine FasL, and even become capable of switching the signal transduction associated with FasL-FasR coupling from the PCD pathway to a tumor growth, proliferative pathway. It seems that the therapeutical use of FasR-FasL (main apoptotic pathway) may represent a new and exciting type of immunotherapy in the treatment of primary childhood glial tumors.
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PMID:Fas (Apo-1, CD95) receptor expression in childhood astrocytomas. Is it a marker of the major apoptotic pathway or a signaling receptor for immune escape of neoplastic cells? 1058 78


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