Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q06643 (non-Hodgkin's lymphoma)
 11,307 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although Fas (APO-1/CD95) is expressed ubiquitously and induces cell death, it is also known to mediate other responses such as inflammation and angiogenesis in vivo. Previously, we have reported that Fas ligation induces selective expression of chemokines (IL-8 and MCP-1) in human astroglioma cells in vitro. In this study, we investigated whether Fas ligation can induce expression of other cytokines. Expression of IL-1alpha, IL-1beta, IL-6, IL-10, IL-12, IFN-beta, IFN-gamma, LT-beta, TGF-beta, TNF-a and TNF-beta mRNA levels in CRT-MG human astroglioma cells upon Fas ligation was investigated using RNase protection assay (RPA). We found that IL-6 mRNA is selectively induced upon Fas ligation, and IL-6 mRNA and protein expression was further investigated using single probe RPA and ELISA. To investigate the in vivo expression of IL-6, human brain specimens were homogenized and ELISA was performed for IL-6 expression. Herein, we demonstrate that: (1) Among these cytokines, only IL-6 was induced upon Fas ligation in a dose- and time-dependent manner; (2) A selective p38 MAP kinase inhibitor, SB202190, and a MEK inhibitor, U0126, suppressed induction of IL-6 mRNA and protein expression by Fas ligation; and (3) Glioblastoma multiforme samples (n = 11) contain significantly higher levels of IL-6 compared to those of control brains (n = 5), which correlate with increased levels of Fas. These results suggest that the Fas-FasL system may play a role in the regulation of tumor growth and survival by inducing the pleiotropic cytokine IL-6.
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PMID:Fas engagement increases expression of interleukin-6 in human glioma cells. 1194 22

The CD95 (Fas) molecule transmits apoptotic signals important in B-cell development and the genesis of B-cell lymphoma. We have investigated the surface and intracellular expression of CD95 in Burkitt's lymphoma (BL) cells, an important non-Hodgkin's lymphoma of B-cell origin. Group I BL cells did not express CD95 at the cell surface, but contained high levels of this receptor in the cytoplasm. In contrast, group III BL cells expressed CD95 intracellularly and at the cell surface. In group I and group III BL cells, cytoplasmic CD95 was localized to the Golgi complex, as assessed by confocal immunofluorescence microscopy and subcellular fractionation followed by immunoblotting. Trafficking through the Golgi complex is regulated by elements within the target protein and cellular sorting mechanisms. CD95 contains candidate signals for interaction with trafficking machinery. Group I BL cells can be induced to upregulate surface expression of CD95 following CD40 ligation and certain group I BL cell lines drift invitro to a group III phenotype, with consequent surface expression of CD95. Taken together, these observations show that CD95 can either be retained in the Golgi complex or exported to the cell surface, and suggest that membrane trafficking has an important and previously unrecognized role in regulating CD95 expression in B lymphocytes.
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PMID:CD95 (Fas) expression is regulated by sequestration in the Golgi complex in B-cell lymphoma. 1213 37

We have previously reported that specific anti-tumour cytotoxic T cells (CTL) can be differentiated from tumour-infiltrating lymphocytes (TIL) in non-Hodgkin's lymphoma. We found that the combination of interleukin (IL)-1, IL-2 and IL-12 was very efficient for expansion of CD8+ T-cell receptor (TCR)alphabeta+ T cells and for development of their ability to specifically lyse tumour cells. In this study, we investigated whether anti-tumour T cells could be generated from the peripheral blood of patients using the culture protocol developed for TIL. Autologous T cells and tumour B cells from five patients were included in this study. It was found that polyclonal anti-tumour cytotoxic effector cells were generated when cultured in the presence of IL-1beta, IL-2 and IL-12. Interestingly, tumour cells were lysed by perforin/granzyme-mediated cytolysis and not by CD95-mediated apoptosis. By performing inhibition experiments, it was observed that both CD8+ and CD4+ T cells were responsible for the cytotoxic effect and that they were able to recognize malignant B cells by either a major histocompatibility complex (MHC)-restricted or MHC-non-restricted mechanism. Intriguingly, in addition to interferon-gamma and tumour necrosis factor-alpha, IL-10 was secreted continuously during culture. The source of patient T cells used for the generation of anti-tumour CTL should be based on the results obtained with peripheral blood lymphocytes and TIL.
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PMID:Differentiation of anti-tumour cytotoxic T lymphocytes from autologous peripheral blood lymphocytes in non-Hodgkin's lymphomas. 1240 81

Killer lymphocytes play a central therapeutic role in graft-versus-leukemia following allogeneic hematopoietic stem cell transplantation (HSCT). The Perforin/Granzyme and FAS/CD95 pathways are of crucial importance in tumor cell elimination by killer cells. In this study, we have examined whether hematological malignancies are resistant to perforin and anti-FAS antibodies. Leukemic cells were studied from 29 patients suffering either from acute or chronic myeloid leukemia (AML or CML), acute or chronic lymphoid leukemia, or non-Hodgkin's lymphoma. An average of 49 vs 5% of specific cell killing was found when using perforin vs anti-FAS antibodies, respectively. Interestingly, resistance towards both perforin and anti-FAS antibodies was found exclusively in leukemic cells from patients with myeloid leukemia. Analysis of leukemic cells from patients with CML, suffering from leukemia relapse after HSCT and given donor lymphocyte infusion (DLI) to induce remission, indicated that the effectiveness of treatment with DLI was not associated with sensitivity of leukemic cells to perforin. In conclusion, resistance towards anti-FAS antibodies is a common phenomenon in leukemia/lymphoma, whereas perforin resistance occurs only in myeloid leukemia. However, as a single parameter, perforin resistance does not appear to be suitable to predict the outcome of DLI.
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PMID:Prevalence and clinical significance of resistance to perforin- and FAS-mediated cell death in leukemia. 1521 73

Apoptosis-related proteins might play an important role in the pathogenesis and sensibility to the chemotherapeutical drugs in patients with non-Hodgkin's lymphoma (NHL). In our study we tried to find out the relation between the expression of CD95/Fas/Apo-1 antigen and clinical outcome of NHL patients. We have measured 24-hour spontaneous apoptosis of peripheral lymphocytes on flow cytometer using specific monoclonal anti-CD95 mouse antibodies in 54 patients aged 19-76 years. Fas expression proved to be a significant prognostic factor in predicting overall survival (OS) because in CD95- (<25%) patients OS was 7% vs. CD95+ with 30%. After grouping of patients by IPI score there was no significant difference between Fas negative and positive cases (IPI 1 - 50% vs. 68%; IPI 2 - 50% both), although in unfavorable risk-groups the OS values differed according to the CD95 expression (IPI 3 - 20% vs. 70%; IPI 4 - 11% vs. 50%). So we conclude, that Apo-1 positive expression appears to be predictive of good overall survival as an independent prognostic parameter, as in association with IPI criteria.
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PMID:Prognostic significance of apoptosis-related CD95 antigen expression in patients with non-Hodgkin's lymphoma. 1585 96

Fas (CD95/APO-1) is a protein that is mainly related to apoptosis of lymphoid cells. The increment of Fas expression is associated with long-term survival in various malignancies. However, there are limited studies regarding the effect of Fas expression on the course and prognosis of non-Hodgkin's lymphoma. The aim of this study was to investigate the significance of immunohistochemical Fas expression on the prognosis of nodal diffuse large B-cell lymphoma. A total of 63 patients with primary nodal diffuse large B-cell lymphoma diagnosed in the Erciyes University Department of Hematology between 1990 and 2003 were included in the study. The median age of the patients was 55 years old (range 19-102 years old). The median follow-up period was 19 months (2-132 months). Histopathological sections were stained immunohistochemically and evaluated by light microscopy for Fas, bcl-2, and p53. Clinical and laboratory parameters including Fas, bcl-2, and p53 positivity, age, sex, performance status, clinical stage, presence of B symptoms, bone marrow involvement, extranodal involvement, and lactic dehydrogenase levels were evaluated to compare overall survival. Complete remission was obtained in 28 patients (44.4%) after first-line chemotherapy. Fas positivity, male gender, good performance status, clinical stage I-II, absence of B symptoms, normal lactic dehydrogenase value, and absence of bone marrow involvement were favorable prognostic factors for complete remission in statistical analysis. Multivariate analysis revealed that positive Fas expression and ECOG performance status were independent prognostic factors for overall survival. Also, Fas-positive patients had significantly prolonged progression-free survival. Immunohistochemical Fas positivity was a favorable prognostic factor for complete remission and overall and progression-free survival in primary nodal diffuse large B-cell lymphoma.
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PMID:Prognostic significance of Fas (CD95/APO-1) positivity in patients with primary nodal diffuse large B-cell lymphoma. 1701 88

Chemotherapy of non-Hodgkin's lymphoma is frequently hampered by drug resistance. The monoclonal antibody rituximab specifically targets the CD20 antigen and sensitizes B-cell lymphoma cells to standard anticancer drugs. In the present investigation, we analyzed, whether a combination of rituximab and artesunate may act in a complementary manner and eventually synergize in tumor cell killing. Artesunate is an anti-malarial drug, which also exerts profound activity towards cancer cells. While rituximab alone was minimally cytotoxic, rituximab increased cytotoxicity to artesunate in Ramos cells. Artesunate induced apoptosis, induced Fas/CD95 expression and the formation of reactive oxygen species (ROS) and resulted in a breakdown of mitochondrial membrane potential. This argues for the involvement of both receptor-driven extrinsic and mitochondrial intrinsic routes of apoptosis. Rituximab increased Fas/CD95 expression and ROS formation and decreased mitochondrial membrane potential ultimately leading to increased apoptosis induced by artesunate. The transcription factors YY1 and Sp1 are upstream regulators of apoptosis by controlling the expression of apoptosis-regulating genes. YY1 and Sp1 were down-regulated and Fas/CD95 was up-regulated by rituximab and artesunate indicating that artesunate activated the Fas/CD95 pathway and that rituximab increased the susceptibility of tumor cells to artesunate-induced apoptosis. Furthermore, rituximab affected the expression of antioxidant genes. The antibody decreased artesunate-induced up-regulation of catalase expression and increased artesunate-induced down-regulation of glutathione S-transferase-phi expression. Manganese-dependent superoxide dismutase expression was not changed by artesunate. Antioxidant proteins may help to detoxify artesunate-induced ROS. Rituximab reversed the artesunate-induced expression changes of antioxidant genes and, hence, reduced the detoxification capacity of Ramos cells. The effects of rituximab on antioxidant genes represent a novel mechanism of rituximab for chemosensitization.
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PMID:Combination treatment of malignant B cells using the anti-CD20 antibody rituximab and the anti-malarial artesunate. 1951 62

Apoptosis-related proteins play an important role in lymphoma cell death during chemotherapy. In our study, we investigated the prognostic significance of CD95, BCL2, and P53 expression in extranodal non-Hodgkin's lymphoma (NHL). We examined 71 patients with extranodal NHL [45 diffuse large B-cell lymphomas (DLBCLs) and 26 mucosa-associated lymphoid tissue lymphomas (MALTLs)], 35 male and 36 female, with a median age of 65.8 years. The most common site of origin was the stomach (N = 31). Paraffin-embedded specimens were analyzed immunohistochemically for CD95, BCL2, and P53 expression. Multivariate analysis revealed that in DLBCLs, positive CD95 and negative BCL2 expression were independent prognostic factors for overall survival. We reached the same conclusion for MALTLs, with positive CD95 and negative P53 expression. In DLBCLs, the 5-year overall survival rate was 71.5% for the CD95-positive cases and 35% for the CD95-negative cases (p = 0.004) and the 5-year overall survival was significantly better in BCL2-negative cases (70.8%) when compared to BCL2-positive cases (37%; p = 0.009). In MALTLs, the 5-year overall survival rate for the CD95-positive and CD95-negative groups was 89.5% and 42.9%, respectively (p = 0.004) and the 5-year overall survival rate was 50% for the P53-positive cases and 88.9% for the P53-negative cases (p = 0.016). In conclusion, positive CD95 expression proved to be a good prognostic factor of overall survival in both extranodal DLBCLs and MALTLs. In contrast, positive expression of BCL2 and P53 was found to be unfavorably associated with survival in extranodal DLBCLs and MALTLs, respectively.
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PMID:Prognostic significance of CD95, P53, and BCL2 expression in extranodal non-Hodgkin's lymphoma. 2035 31


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