UMLS:C0019829 - FACTA Search

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Query: UMLS:C0019829 (Hodgkin's disease)
30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Fas and Fas ligand expression were investigated in twenty two cases of classical Hodgkin's disease (HD) by immunohistochemistry. While Reed-Sternberg (RS) cells in 7/22 (32%) cases expressed Fas ligand, reactive lymphoid cells expressed Fas ligand in only 2 (9%) cases. In 20/22 (91%) cases, the RS cells expressed Fas. A higher proportion of RS cells in the nodular sclerosis subtype expressed Fas as compared to the mixed cellularity subtype. In 18/22 (82%) cases, Fas expression was also noted in the reactive lymphoid cells. In eight cases, the reactive lymphoid cells were also analyzed by flow cytometry and a majority of them were CD4+CD45RO+. Most of these activated T-cells expressed Fas but were negative for Fas Ligand. To investigate the co-expression of Fas and Fas Ligand in the RS cells, six cases were subjected to Fas and Fas ligand immunostaining on consecutive sections. The co-expression was documented in the RS cells in four of six cases. These six cases with expression of both Fas and Fas ligand were investigated for the incidence of apoptosis. There was no statistically significant relationship between expression of Fas on reactive cells, expression of FasL on RS cells and the proportion of apoptotic reactive cells. In all these cases apoptosis was not observed in the RS cells. Thus Fas - FasL interactions may not lead to apoptosis of the RS cells.
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PMID:Expression of Fas and Fas ligand in Hodgkin's disease. 1034 79

Reed-Sternberg (RS) cells and their mononuclear variants, Hodgkin's (H) cells, are considered to be the neoplastic cells of Hodgkin's disease (HD). The cellular origin of H-RS cells remains the subject of considerable controversy, although most recent papers have claimed that H-RS cells are of B cell origin. Recently, however, it has been reported that some H-RS cells express granzyme B, as observed in cytotoxic T cells and/or natural killer cells, which also express CD95 ligand (FasL/APO-1L). In the present study, the expression of CD95L and granzyme B in H-RS cells of HD was investigated. CD95L was detected in H-RS cells in five of nine HD cases (one case of lymphocyte-rich classical HD, two of these cases of nodular sclerosis type, and two of four cases of mixed cellularity type). All three examined HD cell lines expressed CD95L in the cytoplasm, although cell surface expression was seen only in L428 cells. Three HD cases expressed both CD95L and granzyme B. It was concluded that CD95L is frequently expressed in H-RS cells, which is one of their notable characteristics; albeit it seems to be irrespective of cell lineage.
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PMID:CD95 ligand is expressed in Reed-Sternberg cells of Hodgkin's disease. 1035 62

The recently identified decoy receptor 3 (DcR3) binds to FasL and inhibits FasL-induced apoptosis, and is considered to play a role in the immune escape system of neoplastic cells. To examine the involvement of DcR3 in the immune evasions of virus-associated lymphoma, we analyzed the amplification and expression of DcR3, using dot blot and in situ hybridization (ISH), in 45 cases, which included 17 cases with Epstein-Barr virus (EBV)-associated lymphoma (seven pyothorax-associated B-cell lymphomas (PAL); ten natural killer lymphoma (NKL)), seven cases with adult T-cell leukemia lymphoma (ATLL), 13 Hodgkin's disease (eight EBV-associated cases; five non-EBV-associated cases), and eight control cases (three reactive lymphadenopathy; five non-EBV-associated-B-cell lymphoma). EBV-associated PAL and NKL exhibited DcR3 amplification and expression in lymphoma cells. ATLL also showed DcR3 expression and amplification. The cases with DcR3 amplification showed DcR3 expression; however, the expression was confined in the neoplastic cells, but not in the reactive cells. In Hodgkin's disease (HD), DcR3 was expressed only in Hodgkin and Reed-Sternberg giant (H-RS) cells. However, DcR3 was not expressed or amplified in reactive lymphadenopathy. Non-EBV-associated B-cell lymphoma also rarely expressed DcR3, and showed no amplification except in two cases, in which rare expression was present. Our results suggest that EBV and HTLV-I probably use DcR3 to escape from the immune system during lymphomagenesis, or virus-infected lymphoma cells with DcR3 expression might be selected in the multistep tumorigenesis.
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PMID:Amplification and expression of a decoy receptor for fas ligand (DcR3) in virus (EBV or HTLV-I) associated lymphomas. 1109 89

Mammalian cells are capable of committing "active suicide" or apoptosis in response to specialized pathological mechanisms employing a phylogenetically developed intrinsic program of death, triggered by signal transduction through specific receptors. Changes in cellular structure such as: 1) condensation of the nuclear (chromatin) and cytoplasmic structures (especially the mitochondria); 2) blebbing of the cell membrane; 3) characteristic swelling of the endoplasmic reticulum; and 4) fragmentation of the cells in membrane bound apoptotic bodies, are the dramatic signs of total cell destruction. Apoptosis requires energy in the from of ATP, indicating that programmed cell death (PCD), as opposed to necrosis, is an energy dependent, active physiological and pathophysiological phenomenon. During this immunocytochemical study, we observed the presence of PCD in the prenatal thymus and various human neoplastically transformed tissues. During the intrauterine ontogenesis, in thymocytes or resting T lymphocytes, p53 tumor suppressor protein was identified to be a critical mediator of PCD in response to DNA damage. The cellular interaction of immature, cortical thymocytes (characterized by a double positive CD4+CD8+TCRlow immunophenotype-IP) with thymic RE cells induces positive selection of T lymphocytes that recognize, but are not activated, by self-MHC molecules (tolerance induction). Double positive CD4+CD8+CD3- thymocytes undergo FasL-mediated apoptosis, while CD4+CD8+CD3+ cells use the CD3 mediated pathway of PCD. Two step, apoptotic cell death is mainly restricted to the CD4+CD8+TCR dull thymocyte subpopulation. T-lymphocytes which do not undergo positive selection are killed by apoptosis in response to a number of intrinsic and extrinsic factors, such as chemical toxins, viral infections, X- and UV irradiation, mild hyperthermia, the actions of various hormones, extracellular survival factors, calcium ionophores (such as A23187), various chemotherapeutic drugs (adriamycin, actinomycin D, etc) and antibodies directed to the CD3-TCR (T cell receptor) complex. Immature thymocytes also undergo a second selective process, so-called negative selection, when thymic stromal cells eliminate autoreactive T lymphocytes. As a typical model of embryonal neoplasms, we observed 34 childhood PNET/MED tissues samples. A systematic observation for the presence of apoptosis related markers (especially FasR) and cells in PCD was carried out. A strong expression (intensity of staining: "A"--the highest possible; number of stained neoplastic cells: +++ to ++++, between 50% to 90%) of FasR was detected. We also observed 42 childhood glial tumors, divided as follows: 6 pilocytic ASTRs; 14 low grade ASTRs; 16 anaplastic ASTRs; and 6 GBMs. The GBMs represent an end-stage brain tumor IP dedifferentiation of glial origin. During the immunocytochemical screening of these 42 childhood ASTRs, we detected strong expression (intensity of staining: "A"--the highest possible; number of stained cells: ++ to ++++, between 20% to 90%) of FasR, employing 4 microns thick, formalin fixed, paraffin-wax embedded tissue slides. FasR expression was rated high, 70% to 90% on the tumor cells in pylocytic ASTRs, lowered to 50% to 60% on the neoplastic cells in low grade ASTRs, even lower between 30% to 40% in anaplastic ASTRs and significantly lower, between 20% to 35% on the neoplastically transformed cells of GBM tissues. The presence of apoptotic neoplastic cells was also regularly detected in other human adult neoplasms, such as thyroid, pancreatic, hepatocellular, gastric, colon, breast, ovarian, prostata, and renal cell carcinomas, as well as, in Hodgkin and non-Hodgkin lymphomas and some sarcomas. The expression of apoptosis related cell surface molecules on the surface of both neoplastically transformed cells and on tumor cell specific, cytotoxic T lymphocyte (CTL) surfaces (FasR-FasL system) raises a distinct possibility of active PCD induction in CTL by tumor cells. Juxtacrine interactions between CTL and neoplastically transformed cells, coupled with observations that tumor cells can modulate the intracellular, signaling domains of cell surface receptors to elicit responses quite often contrary to the expected, may even provide a way for CTL to enhance the proliferation and dedifferentiation of cancer cells. Adoptive cellular immunotherapies employing CTL raised against autologous neoplastically transformed cells in vitro should be employed in the control of minimal residual disease following surgical resection of the primary malignant growth.
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PMID:The role of apoptosis in normal ontogenesis and solid human neoplasms. 1120 98

Lymphomas were studied in kindreds with autoimmune lymphoproliferative syndrome (ALPS; Canale-Smith syndrome), a disorder of lymphocyte homeostasis usually associated with germline Fas mutations. Fas (CD95/APO-1) is a cell surface receptor that initiates programmed cell death, or apoptosis, of activated lymphocytes. Lymphoma phenotype was determined by immunohistochemistry, frequency of CD3(+)CD4(-)CD8(-) T-cell-receptor alpha/beta cells by flow cytometry, nucleotide sequences of the gene encoding Fas (APT1, TNFRSF6), and the percentage of lymphocytes undergoing apoptosis in vitro. Of 223 members of 39 families, 130 individuals possessed heterozygous germline Fas mutations. Eleven B-cell and T-cell lymphomas of diverse types developed in 10 individuals with mutations in 8 families, up to 48 years after lymphoproliferation was first documented. Their risk of non-Hodgkin and Hodgkin lymphomas, respectively, was 14 and 51 times greater than expected (each P <.001). Investigation of these 10 patients and their relatives with Fas mutations revealed that all had defective lymphocyte apoptosis and most had other features of ALPS. The tumor cells retained the heterozygous Fas mutations found in the peripheral blood and manifested defective Fas-mediated killing. These data implicate a role for Fas-mediated apoptosis in preventing B-cell and T-cell lymphomas. Inherited defects in receptor-mediated lymphocyte apoptosis represent a newly appreciated risk factor for lymphomas.
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PMID:The development of lymphomas in families with autoimmune lymphoproliferative syndrome with germline Fas mutations and defective lymphocyte apoptosis. 1141 80

Lymphoproliferative disorders associated with the Epstein-Barr virus (EBV) include non-Hodgkin's lymphoma, Hodgkin's lymphoma, and "post-transplant lymphoproliferative disorders" (PTLD), which occur with immunosuppression after marrow and organ transplantation. PTLD is characterized by actively proliferating, latently infected EBV(+) B-lymphocytes, and often manifests a rapidly progressive fatal clinical course if the immunosuppression cannot be reversed. Lung transplant recipients are a subset of patients at special risk for developing PTLD. The incidence of PTLD development in these patients has been estimated at 5--10%. Whereas immunologic and antiviral therapy have been moderately effective for treating EBV-associated infections in the lytic phase, they have been less useful in the more common latent phase of the disease. One common treatment for herpesvirus infections has targeted the virus-specific enzyme thymidine kinase (TK). The lack of viral TK expression in EBV(+) tumor cells, due to viral latency, makes anti-viral therapy alone ineffective as an anti-neoplastic therapy, however. We have developed a strategy for the treatment of EBV-associated lymphomas/PTLD using pharmacologic induction of the latent viral TK gene and enzyme in the tumor cells, followed by treatment with ganciclovir. Arginine butyrate selectively activates the EBV TK gene in latently EBV-infected human lymphoid cells and tumor cells. A Phase I/II trial has been initiated, employing an intra-patient dose escalation of arginine butyrate combined with ganciclovir. In six patients with EBV-associated lymphomas or PTLD, all of which were resistant to conventional radiation and/or chemotherapy, this combination produced complete clinical responses in four of six patients, with a partial response occurring in a fifth patient. Pathologic examination in two of three patients demonstrated complete necrosis of the EBV lymphoma, with no residual disease, following a single three-week course of the combination therapy. Possible side-effects of the therapy included nausea and reversible lethargy at the highest doses. One patient suffered acute liver failure, thought to be secondary to release of FasL from the necrotic tumor. Analysis of patient-derived tumor cells in culture demonstrated that arginine butyrate produced selective induction of the EBV TK gene, which then conferred sensitivity to ganciclovir, resulting in tumor apoptosis. Additional patient accrual is sought for further evaluation of this therapy.
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PMID:Epstein--Barr virus post-transplant lymphoproliferative disease and virus-specific therapy: pharmacological re-activation of viral target genes with arginine butyrate. 1149

Against the background of its earliest recognition, programmed cell death (PCD) or apoptosis (A) is presented in its fundamental biological contexts. Techniques of its demonstration are listed. Former original works of the authors encompass designs for genetically engineered oncolytic viruses. Presented here are observations on mesenchymal stromal cells of the bone marrow serving as feeder layers to chronic lymphocytic leukemia (CLL) cells (recently rediscovered elsewhere as subverted "nurse cells" protecting CLL cells from A). A-resistant human melanoma cells are shown to expropriate the Fas ligand to Fas receptor (CD95; APO-1) (FasL-->FasR) system for their autocrine growth loop not only in melanoma cells coexpressing CD95 and its ligand but also in CD95-positive melanoma cells undergoing divisions when exposed to CD95 ligand. Bi-directional A-induction is demonstrated upon the encounter of cytotoxic lymphocytes and targeted tumor cells as exemplified with lymphomas; and chemotherapy-induced A of malignant cells as exemplified by paclitaxel-induced PCD of Reed-Sternberg (RS) cells in a case of chemotherapy-resistant Hodgkin's disease (HD). A list of interventions capable of inducing A in tumor cells is provided. These interventions are of potential therapeutic value. The balance of apoptotic and anti-apoptotic forces in virally infected normal and malignant cells is discussed.
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PMID:Virological and immunological connotations of apoptotic and anti-apoptotic forces in neoplasia. 1149 24

Immunologic abnormalities have been described in patients with Hodgkin lymphoma, including autoimmune hemolytic anemia and immune thrombocytopenic purpura. The concurrent diagnoses of Hodgkin lymphoma and acquired aplastic anemia, however, is extremely rare. We report a 56-year-old Japanese female patient with severe aplastic anemia and increased large granular lymphocytes prior to the recurrence of Hodgkin lymphoma. After being in remission for 10 years from Hodgkin lymphoma, she developed progressive pancytopenia. The large granular lymphocytes (expressed CD3+ CD8+ TCRalphabeta+) had a polyclonal distribution, the serum-soluble FasL concentration was significantly elevated, and bone marrow biopsy showed severely hypocellular bone marrow without infiltration of abnormal lymphocytes. No lymphadenopathy was observed that would suggest a relapse of Hodgkin lymphoma. A diagnosis of aplastic anemia was made, and treatment with corticosteroids and cyclosporine was initiated. Two months later, she suddenly developed celiac and mediastinal lymphadenopathy. She underwent one cycle of chemotherapy before she died of progressive pancytopenia. Autopsy revealed the recurrence of Hodgkin lymphoma, nodular sclerosis in the lymph nodes and markedly hypocellular bone marrow. Although autoimmune disorders are described in Hodgkin lymphoma, our case shows a rare instance of a patient who had aplastic anemia as the first manifestation of a relapse of Hodgkin lymphoma.
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PMID:Hodgkin lymphoma accompanied by aplastic anemia and polyclonal expansion of large granular lymphocytes. 1731 50

The soluble decoy receptor 3 (DcR3) is a member of the TNF receptor superfamily. It is regarded as a decoy receptor released from tumor cells to escape host immune response by neutralizing the cytotoxic and immunomodulatory effects of FasL, LIGHT and TL1A. Overexpression of DcR3 has been observed in several human malignancies; however, only limited information exists on the role of DcR3 in non-Hodgkin lymphoma especially for B-cell origin. In the current study, the expression profile of DcR3 was analyzed by RT-PCR and immunohistochemistry (IHC) in a set of lymphoma cell lines including T-cell and B-cell lymphomas. The result demonstrated that overexpression of DcR3 was detected in most T-cell lymphoma cells, which was consistent with previous reports. Interestingly, overexpression of DcR3 was also detected both in the B-cell lymphoma cell lines and diffuse large B cell lymphoma (DLBCL) patients. DcR3 overexpression was associated with a worse prognosis in DLBCL patients (p=0.05). An in vitro study showed that neutralization of DcR3 increased the percentage of doxorubicin-mediated apoptosis in two B-cell lymphoma cell lines, which indicated the possibility of DcR3 mediated chemo-resistance in B-cell lymphomas. We suggest that overexpression of DcR3 is associated with a worse prognosis in DLBCL and the possible mechanism may act through the increase of chemo-resistance of lymphoma cells.
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PMID:Expression of a soluble decoy receptor 3 in patients with diffuse large B-cell lymphoma predicts clinical outcome. 1869 85

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