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)

Hodgkin lymphoma (HL) is characterized by a minority of neoplastic cells, the so-called Reed-Sternberg (RS) cells and a vast majority of reactive cells. RS cells produce chemokines that can attract subsets of peripheral blood cells into HL tissues. To gain insight in the chemokines involved in HL, 16 chemokines were selected based on their ability to recruit different subsets of cells. Five HL, 5 non-HL-derived cell lines, 22 HL, 5 non-HL and 3 control tissues were analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR). Products for 13 of these 16 chemokines were detected in 1 or more of the cell lines tested. No or only very faint signals were obtained in HL for CXCL12, CCL7 and CCL8, but CXCL10, CCL5, CCL13, CCL17 and CCL22 were highly or differentially expressed in HL cell lines and tissues. Immunohistochemistry was performed with antibodies reactive with the latter 5 chemokines on paraffin sections of 21 cases of HL. CCL17 and CCL22 had the highest signals in RS cells at gene expression and at protein levels. CCL17 was specific for the classic HL subtypes, whereas CCL22 also had low signals in NLP samples, as well as in some non-HL. CXCL10 was expressed in a large proportion of HL cases with a predominant expression in EBV-positive cases. The results indicate that RS cells produce a complex pattern of chemokines that are involved in the recruitment of reactive cells and contribute to the paradox of an extensive but ineffective host immune response.
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PMID:Common and differential chemokine expression patterns in rs cells of NLP, EBV positive and negative classical Hodgkin lymphomas. 1211 99

The t(14;18) is the most common genetic alteration in follicular lymphoma, and is detectable in a subset of diffuse large B-cell lymphomas (DLBCL), resulting in over-expression of the anti-apoptotic protein BCL-2. Although the t(14;18)-induced over-expression of BCL-2 is an important step in lymphomagenesis, this aberration alone is not sufficient to produce malignant lymphoma. Further analysis of these tumors is needed to identify additional genes that might be involved in the genesis of follicular lymphoma and progression to DLBCL. To address this issue, we analyzed the gene expression profiles of four t(14;18)-positive cell lines and two t(11;14)-positive mantle-cell lymphoma cell lines using cDNA microarrays containing 4364 genes, and compared them to the genetic profile of phenotypically purified B-cells obtained from hyperplastic tonsils. A total of 137 genes were differentially expressed by approximately twofold or more in the t(14;18) cell lines relative to tonsillar B-cells. 68 genes were up-regulated, 69 genes were down-regulated, and approximately 20% of the differentially regulated genes had no known function. The up-regulated genes included a number of genes involved in the promotion of cellular proliferation and survival, as well as cell metabolism. Down-regulated genes included mediators of cell adhesion and negative regulators of cell activation and growth. Hierarchical clustering analysis separated the t(14;18) and mantle-cell lines into distinct groups based on their gene expression profiles. We confirmed the differential expression of approximately 80% of selected up- and down-regulated genes identified by microarray analysis by quantitative real-time fluorescence reverse transcriptase polymerase chain reaction (RT-PCR) analysis and/or immunoblotting. This study demonstrates the utility of cDNA microarray analysis for the assessment of global transcriptional changes that characterize t(14;18)-positive cell lines, and also for the identification of novel genes that could potentially contribute to the genesis and progression of non-Hodgkin's lymphomas with this translocation.
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PMID:Microarray analysis of B-cell lymphoma cell lines with the t(14;18). 1216 73

Anaplastic large cell lymphoma (ALCL) with t(2;5)(p23;q35) and Hodgkin disease (HD) share many cellular features, including expression of CD30. We compared gene expression profiles of 4 ALCL (Karpas 299, SU-DHL-1, DEL, SR-786) and 3 HD cell lines and found that BCL3, which encodes a nuclear protein belonging to the I kappa B family of inhibitors of nuclear factor-kappa B (NF-kappa B) transcriptional factors, was expressed at higher levels in ALCL than HD. Northern and Western blotting analyses confirmed the high-level expression of BCL3 in ALCL at both mRNA and protein levels. We established a real-time reverse transcriptase-mediated polymerase chain reaction assay to measure the BCL3 mRNA level and found a predominant level of BCL3 expression in t(2;5)(+) ALCL; the levels of cell lines and clinical materials were comparable to or higher than that of a B-cell chronic lymphocytic leukemia carrying t(14;19)(q32;q13). Southern blotting and fluorescence in situ hybridization disclosed that the BCL3 gene copies were amplified in SU-DHL-1, whereas Karpas 299 carried 4 BCL3 gene loci. The BCL3 gene contains 2 cytosine-guanine dinucleotide (CpG) islands, and the intragenic 3' CpG was entirely demethylated in SU-DHL-1 and DEL. In contrast to HD, in which NF-kappa B was constitutively activated, ALCL cells consistently showed (p50)(2) homodimer binding activity on electrophoretic mobility shift assay. It is suggested that the high-level nuclear Bcl-3 sequesters the (p50)(2) homodimer to the nucleus, which may account for the contradictory effect of CD30 stimulation on ALCL and HD. We propose that BCL3 is overexpressed by genetic and epigenetic modifications, potentially contributing to the development of t(2;5)(+) ALCL.
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PMID:High-level expression of BCL3 differentiates t(2;5)(p23;q35)-positive anaplastic large cell lymphoma from Hodgkin disease. 1286 93

Hepatitis C virus (HCV) is a major cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Studies of HCV replication and pathogenesis have so far been hampered by the lack of an efficient tissue culture system for propagating HCV in vitro. Although HCV is primarily a hepatotropic virus, an increasing body of evidence suggests that HCV also replicates in extrahepatic tissues in natural infection. In this study, we established a B-cell line (SB) from an HCV-infected non-Hodgkin's B-cell lymphoma. HCV RNA and proteins were detectable by RNase protection assay and immunoblotting. The cell line continuously produces infectious HCV virions in culture. The virus particles produced from the culture had a buoyant density of 1.13 to 1.15 g/ml in sucrose and could infect primary human hepatocytes, peripheral blood mononuclear cells (PBMCs), and an established B-cell line (Raji cells) in vitro. The virus from SB cells belongs to genotype 2b. Single-stranded conformational polymorphism and sequence analysis of the viral RNA quasispecies indicated that the virus present in SB cells most likely originated from the patient's spleen and had an HCV RNA quasispecies pattern distinct from that in the serum. The virus production from the infected primary hepatocytes showed cyclic variations. In addition, we have succeeded in establishing several Epstein-Barr virus-immortalized B-cell lines from PBMCs of HCV-positive patients. Two of these cell lines are positive for HCV RNA as detected by reverse transcriptase PCR and for the nonstructural protein NS3 by immunofluorescence staining. These observations unequivocally establish that HCV infects B cells in vivo and in vitro. HCV-infected cell lines show significantly enhanced apoptosis. These B-cell lines provide a reproducible cell culture system for studying the complete replication cycle and biology of HCV infections.
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PMID:Establishment of B-cell lymphoma cell lines persistently infected with hepatitis C virus in vivo and in vitro: the apoptotic effects of virus infection. 1252 48

While most anaplastic lymphoma kinase (ALK)-positive non-Hodgkin lymphomas (NHLs) are of T-cell lineage, a small number of B-lineage tumors with plasmablastic morphology and expression of the full-length ALK protein have been described in the literature. All of these reported tumors lacked the NPM-ALK fusion transcript. There is controversy regarding the existence of ALK fusion-positive B-cell NHL, with many investigators contending that ALK fusions are expressed uniquely in T- or null-cell lymphomas. Here we describe 2 well-characterized cases of ALK-positive B-cell lymphoma expressing the NPM-ALK fusion. Both tumors occurred in pediatric patients and showed poor response to chemotherapy. Each had plasmablastic morphology, showed immunoglobulin A restriction, and was ALK positive and CD30- by immunohistochemistry. One tumor showed the t(2;5)(p23;q35) chromosomal translocation by conventional cytogenetics. Both were positive for NPM-ALK by reverse transcriptase-polymerase chain reaction. Thus, ALK-positive plasmablastic B-cell lymphomas are more heterogeneous at the molecular level than previously recognized.
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PMID:ALK-positive plasmablastic B-cell lymphoma with expression of the NPM-ALK fusion transcript: report of 2 cases. 1281 58

Gastric non-Hodgkin's lymphomas can be divided histologically into mucosa-associated lymphoid tissue (MALT) lymphoma (ML) and diffuse large cell lymphoma (DLCL) with or without evidence of preceding/accompanying ML (DLCL + ML). We studied the incidence of the most frequent structural chromosomal aberration in ML, t(11;18)(q21;q21), and numerical aberrations of seven chromosomes in 36 ML, 39 DLCL + ML and ten gastric DLCL cases, by dual-colour interphase fluorescence in situ hybridization (FISH) and reverse transcriptase polymerase chain reaction (RT-PCR). t(11;18)(q21;q21) was exclusively detected in ML (FISH 22%; RT-PCR 24%), being completely absent in DLCL + ML and DLCL. No other translocations involving 11q21 or 18q21 and other partner chromosomes were detected by FISH. In lymphomas harbouring t(11;18)(q21;q21), this translocation was the sole genetic abnormality. In contrast, 45% of the t(11;18)(q21;q21)-negative ML showed trisomies, especially of chromosome 3 and 18. In DLCL + ML with separate small and large cell components, trisomies were either detected in both components or occurred exclusively in large tumour cells. Our results suggest that ML can be divided in lymphomas characterized by the t(11;18)(q21;q21), which are unlikely to transform into high-grade tumours, and t(11;18)(q21;q21)-negative ML that may develop into DLCL + ML after the acquisition of additional genetic aberrations.
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PMID:Mutual exclusion of t(11;18)(q21;q21) and numerical chromosomal aberrations in the development of different types of primary gastric lymphomas. 1461 61

The quest for an infectious agent that may account for cases of Hodgkin's disease (HD) especially in young adults has proven vain until lately. We have recently reported findings that suggested the presence of measles virus (MV) antigens and MV RNA in the tissues of patients with HD. Support for an association between MV and HD has been provided by recent epidemiological findings relating the occurrence of HD to exposure to measles in pregnancy and the perinatal period. We now present further evidence of this putative association based on immunohistochemical, reverse transcriptase-polymerase chain reaction (RT-PCR) and in situ hybridisation studies (ISH) on HD tissues. Biopsies from 82 (54.3%) of our cohort of 154 patients showed a positive immunostain with at least two of the anti-measles antibodies used. Latent membrane protein-1 immunostaining for Epstein-Barr virus was positive in 46 (31.1%) of the patients examined. Reverse transcriptase-PCR and ISH for measles RNA were positive in seven and 10 of 28 patients, respectively. Preliminary clinicopathological associations between MV and HD are noted in this study, but no causal relationship can be claimed at this stage.
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PMID:Measles virus: evidence of an association with Hodgkin's disease. 1522 78

In the United States, oral cancer accounts for more deaths annually than cervical cancer, leukemias, or Hodgkin's lymphoma. Studies have shown that aberrations of chromosome 18q develop with tumor progression and are associated with significantly decreased survival in head and neck cancer patients. The G-protein-coupled receptor, galanin receptor 1 (GALR1), maps to this region of chromosome 18q. Although the role of GALR1 has been well characterized in neuronal cells, little is known regarding this receptor in non-neuronal cells. In this study, the expression, mitogenic function, and signaling mechanism of GALR1 are investigated in normal and malignant oral epithelial cells. mRNA expression was determined via reverse transcriptase-PCR. Protein quantification was done via immunoblot analysis and enzyme-linked immunosorbent assay. For functional and signaling studies, an inhibitory antibody was generated to the N-terminal ligand binding domain of GALR1. GALR1 protein and mRNA expression and GAL secretion were detected at variable levels in immortalized human oral keratinocytes and human oropharyngeal squamous cell carcinoma cell lines. Upon competitive inhibition of GALR1, proliferation was up-regulated in immortalized and malignant keratinocytes. Furthermore, studies with the inhibitory antibody and U0126, the MAPK inhibitor, show that GALR1 inhibits proliferation in immortalized and malignant keratinocytes by inactivating the MAPK pathway. GALR1s inhibitory effects on proliferation in epithelial cells raises the possibility that inactivation or disregulation of this receptor can lead to uncontrolled proliferation and neoplastic transformation.
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PMID:Galanin receptor 1 has anti-proliferative effects in oral squamous cell carcinoma. 1576 48

Deletions of chromosome 8p are a recurrent event in B-cell non-Hodgkin lymphoma (B-NHL), suggesting the presence of a tumor suppressor gene. We have characterized these deletions using comparative genomic hybridization to microarrays, fluorescence in situ hybridization (FISH) mapping, DNA sequencing, and functional studies. A minimal deleted region (MDR) of 600 kb was defined in chromosome 8p21.3, with one mantle cell lymphoma cell line (Z138) exhibiting monoallelic deletion of 650 kb. The MDR extended from bacterial artificial chromosome (BAC) clones RP11-382J24 and RP11-109B10 and included the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor gene loci. Sequence analysis of the individual expressed genes within the MDR and DNA sequencing of the entire MDR in Z138 did not reveal any mutation. Gene expression analysis and quantitative reverse transcriptase-polymerase chain reaction (QRT-PCR) showed down-regulation of TRAIL-R1 and TRAIL-R2 receptor genes as a consistent event in B-NHL with 8p21.3 loss. Epigenetic inactivation was excluded via promoter methylation analysis. In vitro studies showed that TRAIL-induced apoptosis was dependent on TRAIL-R1 and/or -R2 dosage in most tumors. Resistance to apoptosis of cell lines with 8p21.3 deletion was reversed by restoration of TRAIL-R1 or TRAIL-R2 expression by gene transfection. Our data suggest that TRAIL-R1 and TRAIL-R2 act as dosage-dependent tumor suppressor genes whose monoallelic deletion can impair TRAIL-induced apoptosis in B-cell lymphoma.
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PMID:Characterization of 8p21.3 chromosomal deletions in B-cell lymphoma: TRAIL-R1 and TRAIL-R2 as candidate dosage-dependent tumor suppressor genes. 1605 35

In classic Hodgkin lymphoma (HL) and posttransplantation lymphoproliferative disease (PTLD), 2 malignancies frequently associated with Epstein-Barr virus (EBV), the tumor cells often appear to derive from B-cell receptor (BCR)-deficient and therefore preapoptotic germinal center (GC) B cells. To test whether EBV can rescue BCR-less GC B cells, we infected human tonsillar CD77+ GC B cells in vitro with EBV. More than 60 monoclonal lymphoblastoid cell lines (LCLs) were established. Among these, 28 cell lines did not express surface immunoglobulin (sIg). Two of the sIg-negative cell lines carry obviously destructive mutations that have been introduced into originally functional V(H) gene rearrangements during the process of somatic hypermutation. Quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) showed that in most other lines the sIg deficiency was not simply the result of transcriptional down-regulation, but it was rather due to posttranscriptional defects. These findings strongly support the idea that EBV plays a central role in the pathogenesis of classic HL and PTLD by rescuing BCR-deficient, preapoptotic GC B cells from apoptosis, and that EBV infection renders the cells independent from survival signals normally supplied by a BCR. The monoclonal LCLs represent valuable models for early stages of lymphoma development in classic HL and PTLD.
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PMID:Transformation of BCR-deficient germinal-center B cells by EBV supports a major role of the virus in the pathogenesis of Hodgkin and posttransplantation lymphomas. 1613 68


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