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Query: UMLS:C0079731 (B-cell lymphoma)
 16,671 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fas/APO-1 is a cell-surface protein capable of inducing apoptosis in a variety of cell types upon specific antibody engagement. Antibodies against Fas/APO-1 have been used successfully for the treatment of several lymphoid malignancies in mice. Before apoptosis triggered by anti-Fas can be fully exploited as a clinical therapy, Fas/APO-1 distribution, function, and regulation must be further studied. In this study, we analyzed freshly isolated B-cell and T-cell lymphomas as well as nonhematological tumor cell lines for Fas/APO-1 expression and sensitivity to the growth-inhibitory effects of anti-Fas. Constitutive Fas/APO-1 was expressed at very low levels on only one of eight B-cell lymphomas analyzed. Expression was markedly up-regulated, however, by culture with high-molecular-weight B-cell growth factor (HMW-BCGF). Fas/APO-1 was constitutively expressed on one of two T-cell lymphomas examined at levels comparable to those of activated normal lymphocytes. However, neither the B-cell nor T-cell lymphomas positive for Fas/APO-1 expression were growth inhibited by anti-Fas. Furthermore, in the case of one HMW-BCGF-activated B-cell lymphoma, a significant growth enhancement was observed upon anti-Fas treatment. Nonhematologic tumor cell lines showed a similar spectrum of biologic responses to anti-Fas, being growth inhibited, growth stimulated or unaffected by antibody treatment. In summary, these studies suggest that engagement of Fas/APO-1 may trigger a diverse spectrum of biologic effects not unlike other members of the nerve growth factor receptor/tumor necrosis factor receptor superfamily.
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PMID:Fas/APO-1 expression and function on malignant cells of hematologic and nonhematologic origin. 750 10

The Fas/Apo-1 receptor is an integral membrane protein that transduces apoptotic signals upon binding to its natural ligand or to specific antibodies. Loss of Fas/Apo-1 receptor leads in (lpr,lpr) mice to a nonmalignant accumulation of abnormal T-cells very probably due to the lack of induction of apoptosis in peripheral T-cells. It has been reported that soluble forms of Fas/Apo-1 receptor that may interfere with apoptotic signaling occur in patients suffering from various forms of lymphoid neoplasms. Therefore, we wished to investigate whether the loss of proper homeostatic regulation through Fas/Apo-1 receptor mediated apoptosis could influence the process of lymphomagenesis. To this end, we performed two experiments (i) we infected (lpr,lpr) animals with Moloney Murine Leukemia Virus (MoMuLV) that causes T-cell lymphoma in mice and (ii) we crossed (lpr,lpr) animals with E mu L-myc transgenic mice that are prone to develop T- and B-cell lymphoma due to deregulated expression of the L-myc transgene by the immunoglobulin enhancer E mu. We find that infection with MoMuLV did not accelerate the formation of lymphoid neoplasms in (lpr,lpr) mice when compared to infected normal animals. However, E mu L-myc/(lpr,lpr) animals that constitutively express the L-myc transgene in the lymphoid lineage clearly show accelerated formation of T- and B-cell lymphoma when compared to normal E mu L-myc transgenics. These data demonstrate that in cooperation with particular oncogenes impairment of Fas/Apo-1 receptor function can indeed affect and modulate the process of tumor formation.
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PMID:Loss of Fas/Apo-1 receptor accelerates lymphomagenesis in E mu L-MYC transgenic mice but not in animals infected with MoMuLV. 778 89

Fas (CD95) and its ligand are central regulatory molecules in hematopoietic cells. Previous studies have suggested a role for Fas in the regulation of tumor progression, but Fas has not yet been conclusively identified as a tumor suppressor. Fas-deficient individuals lack malignant tumors, perhaps because of regulation by T cells. To investigate such a possibility, mice deficient in both T cells and Fas were generated, and they were found to develop severe B cell dysregulation characterized by malignant, lethal B cell lymphoma. Lymphoma arose from a monoclonal B220+CD19-CD5-CD23- B cell secreting immunoglobulin M, kappa rheumatoid factor. In contrast, animals containing alpha beta T cells, gamma delta T cells, and/or functional Fas suppressed the development of lymphoma. These data indicate that Fas functions as a tumor suppressor, and identifies roles for both alpha beta T cells and gamma delta T cells in Fas-independent tumor regulation.
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PMID:A tumor-suppressor function for Fas (CD95) revealed in T cell-deficient mice. 906 31

Dendritic cells form a system of leukocytes specialized to stimulate resting T cells in vivo. Dendritic cells are crucial for the initiation of primary immune responses of both helper and cytotoxic T lymphocytes, and thus act as 'nature's adjuvant'. The manifold specializations underlying this in vivo immunostimulatory function are becoming increasingly clear. Methods have been developed to generate large numbers of dendritic cells from hematopoietic precursors in vitro. These techniques now allow molecular studies as well as the use of antigen-charged dendritic cells to vaccinate patients against tumors (e.g. B-cell lymphoma or melanoma) and infection (e.g. HIV-1). Recent data suggest that besides the classical immunostimulatory dendritic cells which belong to the myeloid lineage, there exist regulatory dendritic cells related to the lymphoid lineage. These lymphoid-derived dendritic cells which at least in part express Fas-ligand appear to be involved in the induction of central as well as peripheral tolerance, and in the future might allow a novel approach to induce tolerance in transplantation, autoimmunity, and allergy.
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PMID:Dendritic cells: from ignored cells to major players in T-cell-mediated immunity. 910 85

We recently reported the successful use of retinoic acids in the treatment of refractory lymphoma. The biologic determinants predicting response of lymphomas to retinoic acid remain unknown. This study was conducted to explore this question using in vitro models. Sensitivity of representative lymphoma cells to 13-cis-retinoic acid was determined. Sensitive and resistant cell lines were then compared for their baseline and/or retinoic-acid-regulated expression of total cellular retinoic acid binding protein, retinoic acid receptor (RAR)-alpha, RAR-beta, RAR-gamma mRNA, retinoid X receptor (RXR)-alpha, RXR-beta, RXR-gamma mRNA, transforming growth factor (TGF)-beta 1 and TGF-beta 1 receptors, and Fas (Apo-I) mRNA. The results showed that four of five T, two of three Hodgkin's, and none of six B cell lymphoma cell lines were sensitive (IC30 < 1.5 mmol/L) to 13-cis-retinoic acid. Further analyses revealed several of the above-mentioned parameters may be relevant to retinoic acid sensitivity. Baseline expression of TGF-beta 1 receptors was present in all of the five sensitive cell lines examined, but in only one of the four resistant cell lines. The correlation of Fas expression and retinoic acid sensitivity was good for B cell lines, but not apparent for T cell or Hodgkin's cell lines. On exposure to retinoic acid, an immediate and prolonged upregulation of RAR-alpha mRNA expression, lasting for more than 12 hours, occurred in all sensitive cell lines, but only minimal or transient induction was seen in resistant cells. Together, these data suggested that; 1) retinoic acid has a preferential effect on T cell and Hodgkin's lymphoma cell lines; 2) autoregulation of RAR-alpha by retinoic acids, and the presence of TGF-beta 1 receptors may be relevant to the response of lymphomas to treatment with retinoic acids.
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PMID:Factors associated with the therapeutic efficacy of retinoic acids on malignant lymphomas. 926 57

Fas (Apo-1/CD95) ligand (FasL) is a cytotoxic molecule used by T lymphocytes and natural killer cells for target-cell killing and by nonmalignant and malignant cells in the suppression of immune responses. In this study, FasL expression in B- and T-cell non-Hodgkin's lymphomas was investigated by paraffin immunohistochemical analysis. FasL expression was found to be weak in nonaggressive lymphomas (chronic lymphocytic leukemia/small lymphocytic lymphoma, lymphoplasmacytoid lymphoma, Grade 1 follicular center cell lymphoma) and mantle cell lymphoma but strong in aggressive B-cell lymphomas (diffuse large B-cell lymphoma, Burkitt's-lymphoma). Precursor B-lymphoblastic lymphomas were more heterogeneous, with expression varying from weak to strong. In T-cell lymphomas (anaplastic large-cell lymphoma; peripheral T-cell lymphoma, unspecified), strong FasL expression was observed. Apparently, FasL expression is not limited to neoplasms derived from T cells or natural killer cells, and it might play a supporting role in the progression of non-Hodgkin's lymphomas.
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PMID:Fas ligand expression in nodal non-Hodgkin's lymphoma. 957 88

Upon transforming growth factor-beta (TGF-beta) treatment, Ramos cells, a B-cell lymphoma cell line, undergo apoptosis, as measured by annexin V labeling, DNA fragmentation, and propidium iodide staining. Apoptosis could be observed by 24 h after TGF-beta exposure and occurred before the development of a significant blockage of cell cycle progression. TGF-beta-mediated apoptosis was also accompanied by a strong induction of caspase-3 subfamily activity. Incubation of cells with the caspase inhibitor Z-VAD.FMK at 20 microM, but not at 10 microM, prevented TGF-beta-induced apoptosis from occurring. By comparison, caspase-3 subfamily activity was 87% inhibited at 10 microM Z-VAD.FMK and completely inhibited at 20 microM. Because of TGF-beta's well-established role of regulating gene transcription, the mRNA levels for proteins associated with apoptosis (Fas- and Fas-associated proteins, Bcl-2 family members, IAP proteins, and I kappa B) were also studied. After 24 h of TGF-beta treatment, the most significant mRNA changes occurred with Bcl-XL (two-fold decrease) and Bik (twofold increase). TGF-beta treatment also resulted after 48 h in a fivefold decrease in Bcl-XL protein levels, based on immunoblotting analysis. Therefore, TGF-beta-mediated apoptosis involves the activation of caspases. In addition, TGF-beta transcriptionally regulates Bcl-2 family members, Bcl-XL and Bik, to further influence the apoptosis process.
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PMID:Transforming growth factor-beta-mediated apoptosis in the Ramos B-lymphoma cell line is accompanied by caspase activation and Bcl-XL downregulation. 966 22

The defects in lymphocyte apoptosis that underlie the autoimmune lymphoproliferative syndrome (ALPS) are usually attributable to inherited mutations of the CD95 (Fas) gene. In this report, we present the histopathological and immunophenotypic features seen in the lymph nodes (n = 16), peripheral blood (n = 10), bone marrow (n = 2), spleen (n = 3), and liver (n = 2) from 10 patients with ALPS. Lymph nodes showed marked paracortical hyperplasia. Interfollicular areas were expanded and populated by T cell receptor-alphabeta CD3+ CD4-CD8- (double-negative, DN) T cells that were negative for CD45RO. CD45RA+ T cells were increased in all cases studied. The paracortical infiltrate was a result of both reduced apoptosis and increased proliferation, as measured by in situ detection of DNA fragmentation and staining with MIB-1, respectively. The paracortical proliferation may be extensive enough to suggest a diagnosis of malignant lymphoma. Many of the paracortical lymphocytes expressed markers associated with cytotoxicity, such as perforin, TIA-1, and CD57. CD25 was negative. In addition, most lymph nodes exhibited florid follicular hyperplasia, often with focal progressive transformation of germinal centers; in some cases, follicular involution was seen. A polyclonal plasmacytosis also was present. The spleens were markedly enlarged, more than 10 times normal size. There was expansion of both white pulp and red pulp, with increased DN T cells. DN T cells also were observed in liver biopsies exhibiting portal triaditis. In the peripheral blood, the T cells showed increased expression of HLA-DR and CD57 but not CD25. CD45RA+ T cells were increased in the four cases studied. Polyclonal B cell lymphocytosis with expansion of CD5+ B cells was a characteristic finding. Taken together, the histopathological and immunophenotypic findings, particularly in lymph nodes and peripheral blood, are sufficiently distinctive to suggest a diagnosis of ALPS. Of note, two affected family members of one proband developed lymphoma (T-cell-rich B-cell lymphoma and nodular lymphocyte predominance Hodgkin's disease, respectively).
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PMID:Pathological findings in human autoimmune lymphoproliferative syndrome. 981 46

Treatment of B cell lymphoma patients with MoAbs specific for the common B cell marker (CD20) has shown a good overall response rate, but the number of complete remissions is still very low. The use of MoAbs coupled to radioisotopes can improve the results, but induces undesirable myelodepression. As an alternative, we proposed to combine the specificity of MoAbs with the immunogenicity of T cell epitopes. We have previously shown that an anti-Ig lambda MoAb coupled to an MHC class II-restricted universal T cell epitope peptide P2 derived from tetanus toxin induces efficient lysis of a human B cell lymphoma by a specific CD4+ T cell line. Here we demonstrate that the antigen presentation properties of the MoAb peptide conjugate are maintained using a MoAb directed against a common B cell marker, CD19, which is known to be co-internalized with the B cell immunoglobulin receptor. In addition, we provide evidence that B cell lysis is mediated by the Fas apoptosis pathway, since Fas (CD95), but not tumour necrosis factor receptor (TNFr) or TNF-related receptors, is expressed by the target B cells, and FasL, but not perforin, is expressed by the effector T cells. These results show that B cell lymphomas can be 'foreignized' by MoAb-peptide P2 conjugates directed against the common B cell marker CD19 and eliminated by peptide P2-specific CD4+ T cells, via the ubiquitous Fas receptor. This approach, which bridges the specificity of passive antibody therapy with an active T cell immune response, may be complementary to and more efficient than the present therapy results with unconjugated chimeric anti-CD20 MoAbs.
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PMID:An anti-CD19 antibody coupled to a tetanus toxin peptide induces efficient Fas ligand (FasL)-mediated cytotoxicity of a transformed human B cell line by specific CD4+ T cells. 982 73

The changes of phospholipase D (PLD) activity were investigated during the courses of apoptotic process induced by tumor necrosis factor (TNF)-alpha or anti-Fas/Apo1 antibody in human premyelocyte HL-60 and murine B cell lymphoma A20 cells. The treatment of recombinant TNF-alpha to HL-60 cells resulted in the increased PLD activity as determined by the phosphatidylethanol formation in the presence of 1% ethanol. The enhancement of PLD activity was also observed in the anti-Fas/Apo1 monoclonal antibody-treated A20 cells. However, the activity of PLD was maximized when HL-60 and A20 cells were treated with either TNF-alpha or anti-Fas/Apo1 monoclonal antibody for 6 h. Both TNF-alpha and anti-Fas/Apo1 monoclonal antibody increased PLD activity in a dose-dependent manner up to 200 U/ml and 200 ng/ml, respectively. When the intracellular activity of protein kinase C (PKC) was interrupted by treatment of calphostin-C, both the PLD activation and the apoptosis induced by TNF-alpha and anti-Fas/Apo1 monoclonal antibody appeared to be inhibited. Since PKC is reported to activate PLD, the results indicate that the intracellular signaling cascade via PLD may play a role in the induction of apoptosis induced by TNF-alpha and anti-Fas/Apo1 monoclonal antibody.
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PMID:Changes of phospholipase D activity in TNF-alpha and anti-Fas/Apo1 monoclonal antibody induced apoptosis in HL-60 and A20 cells. 987 18


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