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)

Acquired immunodeficiency syndrome (AIDS)-related non-Hodgkin's lymphomas (AIDS-NHLs) consistently derive from B cells, are histologically heterogeneous, and are associated with distinct molecular pathways depending upon histology. Recently, it has been proposed that inactivating mutations of the bax death agonist may contribute to the pathogenesis of human tumors. In particular, among B-cell malignancies, BAX mutations have been detected at a certain frequency in Burkitt lymphomas. This study is aimed at defining the status of the BAX gene throughout the clinicopathologic spectrum of AIDS-NHL (n = 54), including AIDS-related Burkitt lymphoma (n = 14), AIDS-related Burkitt-like lymphoma (n = 8), AIDS-related diffuse large cell lymphoma (n = 15), AIDS-related primary central nervous system lymphoma (n = 6), and AIDS-related primary effusion lymphoma (n = 11). All 6 BAX exons and flanking sequences were subjected to mutational analysis by polymerase chain reaction-single strand conformation polymorphism followed by DNA direct sequencing of positive cases. Mutations of BAX among AIDS-NHL were restricted to a cell line of AIDS-related primary effusion lymphoma, which harbored a frameshift mutation causing the introduction of a proximal stop codon. All other AIDS-NHL displayed wild-type BAX alleles. In order to investigate whether BAX inactivation in AIDS-NHL may occur through mechanisms other than gene mutation, bax protein expression was investigated by Western blot analysis or immunohistochemistry in selected cases. All AIDS-NHL analyzed expressed normal bax proteins. Overall, this study indicates that deregulation of apoptotic control in AIDS-NHL is not caused by BAX alterations. Genes Chromosomes Cancer 27:177-182, 2000.
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PMID:Mutation of BAX occurs infrequently in acquired immunodeficiency syndrome-related non-Hodgkin's lymphomas. 1061 6

High-dose chemotherapy with autologous bone marrow or peripheral blood stem cell transplantation has gained widespread acceptance for the treatment of certain malignancies. Since the introduction of this therapy in 1988 we have treated 272 patients. Indications for high-dose chemotherapy were high-risk large cell lymphoma and lymphoblastic or Burkitt lymphoma in first remission (73 patients), non-Hodgkin's lymphoma in chemosensitive relapse (65 patients), Hodgkin's lymphoma in relapse (52 patients), germ cell tumours with inadequate response to chemotherapy (34 patients), multiple myeloma (29 patients), and other malignancies (19 patients). Treatment mortality was 1.8%. The 3-year event-free survival and overall survival for all patients were 48 and 61% respectively. High-dose chemotherapy with autologous stem cell transplantation has become a safe procedure and is considered the treatment of choice for relapsed large cell lymphoma, relapsed Hodgkin's disease, stage II or III multiple myeloma, and germ cell tumours with inadequate response to cisplatin-based chemotherapy. In other situations, including aggressive lymphoma with risk factors, acute leucaemia or breast cancer, the superiority of high-dose over conventional chemotherapy remains to be proven. Patients with such diseases should not receive high-dose chemotherapy outside a controlled clinical study.
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PMID:[High-dose chemotherapy with autologous bone marrow transplantation: 11 years' experience in Zurich]. 1068 81

Chromosomal rearrangements observed in T-cell prolymphocytic leukemia involve the translocation of one T-cell receptor gene to either chromosome 14q32 or Xq28, deregulating the expression of cellular protooncogenes of unknown function, such as TCL1 or its homologue, MTCP1. In the human hematopoietic system, TCL1 expression is predominantly observed in developing B lymphocytes, whereas its overexpression in T cells causes mature T-cell proliferation in transgenic mice. In this study, using a newly generated monoclonal antibody against recombinant TCL1 protein, we extended our analysis mainly by immunohistochemistry and also by fluorescence-activated cell sorting and Western blot to a large tumor lymphoma data bank including 194 cases of lymphoproliferative disorders of B- and T-cell origin as well as reactive lymphoid tissues. The results obtained show that in reactive lymphoid tissues, TCL1 is strongly expressed by a subset of mantle zone B lymphocytes and is expressed to a lesser extent by follicle center cells and by scattered interfollicular small lymphocytes. In B-cell neoplasia, TCL1 was expressed in the majority of the cases, including lymphoblastic lymphoma, chronic lymphocytic leukemia, mantle cell lymphoma, follicular lymphoma, Burkitt lymphoma, diffuse large B-cell lymphoma (60%), and primary cutaneous B cell lymphoma (55%). TCL1 expression was observed in both the cytoplasmic and nuclear compartments, as confirmed by Western blot analysis. Conversely, TCL1 was not expressed in Hodgkin/Reed-Sternberg cells, multiple myelomas, marginal zone B-cell lymphomas, CD30+ anaplastic large cell lymphoma, lymphoblastic T-cell lymphoma, peripheral T-cell lymphoma, and mycosis fungoides. These data indicate that TCL1 is expressed in more differentiated B cells, under both reactive and neoplastic conditions, from antigen committed B cells and in germinal center B cells and is down-regulated in the latest stage of B-cell differentiation.
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PMID:Regulation of TCL1 expression in B- and T-cell lymphomas and reactive lymphoid tissues. 1078 66

LL2, an anti-CD22 monoclonal antibody against B-cell lymphoma, was covalently linked to the amphibian ribonuclease, onconase, a member of the pancreatic RNase A superfamily. LL2 increased in vitro potency (10 000-fold) and specificity against human Daudi Burkitt lymphoma cells while decreasing systemic toxicity of onconase. Monensin further increased potency of LL2-onconase on Daudi cells (IC(50), 20 and 1.5 pM, absence and presence of monensin, respectively). A 1-hour exposure to LL2-onconase was sufficient to kill Daudi cells in culture. These favorable in vitro properties translated to significant antitumor activity against disseminated Daudi lymphoma in mice with severe combined immunodeficiency disease. In mice inoculated with tumor cells intraperitoneally (ip), LL2-onconase (100 microg 5 times ip every day) increased the life span of animals with minimal disease 200%. The life span of mice with advanced disseminated Daudi lymphoma (tumor cells inoculated intravenously) was increased 135%. Mice injected with LL2-onconase tolerated a dose as high as 300 mg/kg. Because both onconase and LL2 are in clinical trials as cancer therapeutics, the covalently linked agents should be considered for treatment of non-Hodgkin lymphoma.
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PMID:Potent and specific antitumor effects of an anti-CD22-targeted cytotoxic ribonuclease: potential for the treatment of non-Hodgkin lymphoma. 1115 33

This study was aimed at defining the histogenesis of the pathologic spectrum of lymphoma arising in the context of human immunodeficiency virus (HIV) infection. Toward this aim, 87 AIDS-related non-Hodgkin lymphomas (AIDS-NHL) and 16 Hodgkin lymphomas arising in HIV+ patients (HIV-HL) were comparatively analyzed for the expression pattern of several B-cell histogenetic markers, including BCL-6 (expressed by centroblasts and centrocytes), MUM1/IRF4 (expressed by late centrocytes and post-germinal center [GC] B cells), and CD138/syn-1 (expressed by post-GC B cells). Expression of MUM1, BCL-6, and syn-1 segregated 3 major phenotypic patterns among AIDS-NHL and HIV-HL: (1) the BCL-6+/MUM1-/syn-1- pattern, selectively clustering with a large fraction of AIDS-Burkitt lymphoma (17 of 19) and of systemic AIDS-diffuse large cell lymphoma (12 of 16); (2) the BCL-6-/MUM1+/syn-1- pattern, associated with a fraction of AIDS-immunoblastic lymphoma (8 of 24); and (3) the BCL-6-/MUM1+/syn-1+ pattern, associated with systemic and primary central nervous system immunoblastic lymphoma (14 of 24) and with primary effusion lymphoma (10 of 10), plasmablastic lymphoma of the oral cavity (7 of 7), and HIV-HL (15 of 16). Analysis of nonneoplastic lymph nodes showed that the 3 phenotypic patterns detected in AIDS-NHL and HIV-HL correspond to distinct stages of physiologic B-cell development-centroblasts (BCL-6+/MUM1-/syn-1-), late GC/early post-GC B cells (BCL-6-/MUM1+/syn-1-), and post-GC B cells (BCL-6-/MUM1+/syn-1+). Expression of the Epstein-Barr virus-encoded latent membrane protein-1 clustered with the BCL-6-/MUM1+/syn-1+ profile throughout the clinicopathologic spectrum of AIDS-NHL and HIV-HL. Overall, these results define novel histogenetic subsets of AIDS-NHL and HIV-HL and may provide novel tools for refining the diagnosis of these disorders.
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PMID:Expression profile of MUM1/IRF4, BCL-6, and CD138/syndecan-1 defines novel histogenetic subsets of human immunodeficiency virus-related lymphomas. 1115 93

Studies of lymphoid neoplasms occurring in normal or genetically engineered mice have revealed parallels and differences to non-Hodgkin lymphomas (NHL) of humans. Some mouse lymphomas have strong histologic similarities to the human NHL subsets including precursor B- and T-cell lymphoblastic, small lymphocytic, splenic marginal zone, and diffuse large-cell B-cell lymphomas (DLCL); whether molecular parallels also exist is under study. Others mouse types such as sIg+ lymphoblastic B-cell lymphoma have no histologic equivalent in human NHL even though they share molecular deregulation of BCL6 with human DLCL. Finally, Burkitt lymphoma does not appear to occur naturally in mice, but it can be induced with appropriately engineered transgenes.
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PMID:Non-Hodgkin lymphomas of mice. 1135 82

Polycomb-group (PcG) proteins, such as BMI-1 and EZH2, form multimeric gene-repressing complexes involved in axial patterning, hematopoiesis, and cell cycle regulation. In addition, BMI-1 is involved in experimental lymphomagenesis. Little is known about its role in human lymphomagenesis. Here, BMI-1 and EZH2 expression patterns are analyzed in a variety of B-cell non-Hodgkin lymphomas (B-NHLs), including small lymphocytic lymphoma, follicular lymphoma, large B-cell lymphoma, mantle-cell lymphoma, and Burkitt lymphoma. In contrast to the mutually exclusive pattern of BMI-1 and EZH2 in reactive follicles, the neoplastic cells in B-NHLs of intermediate- and high-grade malignancy showed strong coexpression of BMI-1 and EZH2. This pattern overlapped with the expression of Mib-1/Ki-67, a marker for proliferation. Neoplastic cells in B-NHL of low-grade malignancy were either BMI-1(low)/EZH2(+) (neoplastic centroblasts) or BMI-1(low)EZH2(-) (neoplastic centrocytes). These observations show that low-, intermediate-, and high grade B-NHLs are associated with increased coexpression of the BMI-1 and EZH2 PcG proteins, whose normal expression pattern is mutually exclusive. This expression pattern is probably caused by a failure to down-regulate BMI-1 in dividing neoplastic cells, because BMI-1 expression is absent from normal dividing B cells. These observations are in agreement with findings in studies of Bmi-1 transgenic mice. The extent of BMI-1/EZH2 coexpression correlated with clinical grade and the presence of Mib-1/Ki-67 expression, suggesting that the irregular expression of BMI-1 and EZH2 is an early event in the formation of B-NHL. This points to a role for abnormal PcG expression in human lymphomagenesis. (Blood. 2001;97:3896-3901)
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PMID:Coexpression of BMI-1 and EZH2 polycomb-group proteins is associated with cycling cells and degree of malignancy in B-cell non-Hodgkin lymphoma. 1138 32

Hodgkin disease (HD) represents a malignant lymphoma in which the putative malignant Hodgkin and Reed-Sternberg cells are rare and surrounded by abundant reactive nonmalignant cells. It has been suggested that cytokines such as interleukin-6 (IL-6) are involved in the pathogenesis of the disease. The expression of the IL-6 receptor (IL-6R) complex and its link to the activation of signal transducers and activators of transcription (STAT) molecules in HD cell lines was investigated. Gel retardation and Western blot analyses revealed a high level of constitutively activated STAT3 in 5 of 7 HD cell lines, which could not be detected in Burkitt lymphoma cell lines. Different levels of IL-6R protein were measured in various HD cell lines: L428 and Dev cells were characterized by very low levels of gp80 and gp130, on KMH2 cells only gp130 but no gp80 was detected, whereas L540, L591, HDLM2, and L1236 were positive for both gp80 and gp130, suggesting a possible autocrine stimulation of STAT3. However, a further increase in STAT3 activation on IL-6 or IL-6/soluble IL-6R stimulation was not observed. Neutralizing monoclonal antibodies against IL-6, gp80, gp130, or both receptor subunits did not affect the proliferation or the constitutive activation of STAT molecules in HD cell lines. However, the tyrosine kinase inhibitor AG490 blocked the constitutive activation of STAT3 and inhibited spontaneous growth of HD tumor cells. The evidence suggests abnormal STAT signaling and growth regulation in Hodgkin cell lines. (Blood. 2001;98:762-770)
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PMID:STAT3 is constitutively activated in Hodgkin cell lines. 1146 77

Tc-99m sestamibi (MIBI) has been used as a tumor-seeking agent. However, its role in detecting lymphomas has not been widely investigated. The aim of the present study was to determine the uptake and clearance characteristics of Tc-99m MIBI in vincristine-resistant lymphoma cell lines. In addition, thallium-201 (Tl-201) and gallium-67 (Ga-67) uptake and clearance characteristics were evaluated for comparison with Tc-99m MIBI. Drug-resistant lymphoma cell lines (monocyte-like, histiocytic lymphoma, human; B-lymphoma cell line, American Burkitt lymphoma, lymphoblastoid, human; Hodgkin's disease, lymphoid, human) were selected by multistep vincristine treatment up to 50 nM. After incubation of the radiotracers, Tc-99m MIBI, Tl-201 and Ga-67, in medium for 0, 10, 20, 30, 60 or 120 min, the uptake and clearance of each radiotracer were measured in the drug-resistant lymphoma cell lines. In addition, P-glycoprotein expression was determined by immunohistochemical study. In a comparison of the three radiotracers, the uptake of Tc-99m MIBI was the greatest in the studied wild-type lymphoma cell lines. Tc-99m MIBI uptake was much lower in drug-resistant tumor cell lines than in non-resistant cell lines. On the other hand, the uptake characteristics of Tl-201 did not differ between drug-resistant and non-resistant cells. Immunohistochemistry analyses of Ab-1 or JSB indicated that tumor cells expressed MDR-1 protein in all three cell lines. Tc-99m MIBI is a good radiotracer for detecting drug resistance in lymphoma cell lines.
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PMID:Comparison of the uptake and clearance of Tc-99m MIBI, Tl-201 and Ga-67 in drug-resistant lymphoma cell lines. 1152 May 98

A rapid increase in the incidence of non-Hodgkin lymphoma (NHL) has been reported in many countries. Exposure to certain pesticides or organochlorines has been shown to be a risk factor. Epstein-Barr virus (EBV) is a human herpesvirus that has been associated with some subgroups of NHL, such as Burkitt lymphoma and lymphomas related to severe immunosuppression. In this study we measured concentrations of dioxins and dibenzofurans in 33 NHL cases and 39 surgical controls. For 23 of the cases and 32 of the controls EBV titers were also available. Median titer of antibodies to EBV early antigen (EA) IgG was higher in patients than in controls. Concentrations of dioxins and dibenzofurans were divided into two groups according to the median concentration for the controls. Unconditional logistic regression analysis was performed adjusting for sex, age, and body mass index. For several higher chlorinated congeners increased risk was found for patients in the high-concentration and high-titer group. For toxic equivalency factor >27.79 and EA>80 an odds ratio of 2.8 with 95% confidence interval 0.52-18 was calculated. These results indicated that current exposure to certain organochlorines in combination with EBV might increase the risk for NHL.
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PMID:Adipose tissue concentrations of dioxins and dibenzofurans, titers of antibodies to Epstein-Barr virus early antigen and the risk for non-Hodgkin lymphoma. 1168 93


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