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)

A new cell line, SUP-HD1, was established from the pleural effusion of a patient with nodular sclerosing Hodgkin's disease (NSHD). The SUP-HD1 cells had the characteristic morphology of Reed-Sternberg cells and contained acid phosphatase and nonspecific esterase. The cells lacked the Epstein-Barr virus (EBV) genome and reacted with monoclonal antibodies (MoAbs) against CD15 (Leu-M1), CD25 (Tac), CD71 (OKT9), Ki67, and HLA-Dr. However, the SUP-HD1 cells were nonreactive with MoAbs that specifically identify T lymphocytes, B lymphocytes, and macrophage/myeloid cells. Karyotype analysis of the cell line showed clonal abnormalities involving 1p13, 7p15, 8q22, and 11q23, chromosomal locations, at which breakpoints have been reported in HD. Southern blot analysis demonstrated rearrangement of the immunoglobulin heavy chain and kappa light chain genes as well as the gene for the beta chain of the T-cell receptor (TCR). Transcriptional analysis showed expression of RNAs for kappa light chain, interferon-gamma (IFN-gamma), and interleukin-2 receptor (IL-2R) but not IL-2. The SUP-HD1 cells lacked cytoplasmic and surface immunoglobulin heavy chain, but a small amount of cytoplasmic kappa light chain was detected. The presence of nuclear factor kappa B (NF kappa B), a B-lymphocyte-associated transcription factor, was demonstrated in stimulated and unstimulated cells. In addition, the SUP-HD1 cell line, produced IFN-gamma, a T-lymphocyte-associated lymphokine. Based on these data, the SUP-HD1 cells appear to be aberrant lymphocytes with characteristics of both activated B and T lymphocytes. Elaboration of lymphokines such as IFN-gamma by the malignant cells may represent one explanation for the unique clinical and pathologic features of HD.
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PMID:SUP-HD1: a new Hodgkin's disease-derived cell line with lymphoid features produces interferon-gamma. 232 24

The t(2;5) (p23;q35) chromosomal translocation has been found in a high proportion of lymph node-based CD30+ large cell lymphomas of T-cell lineage. This translocation is believed to result in the expression of a fusion protein containing the catalytic domain of anaplastic lymphoma kinase (ALK) under the control of the promoter for nucleophosmin, a nucleolar phosphoprotein. Expression of ALK activity, which does not normally occur in lymphocytes, is postulated to be involved in the pathogenesis of lymphomas bearing the t(2;5) translocation. Several primary cutaneous lymphoproliferative disorders and Hodgkin's disease are also known to contain CD30+ large lymphoid cells. To determine the role of the t(2;5) translocation in these diseases, we developed a DNA-based polymerase chain reaction (PCR)/Southern blot assay to detect this translocation at the genomic level in lymphomatoid papulosis (14 cases), primary cutaneous CD30+ large cell lymphoma of T-lineage (10 cases) and Hodgkin's disease (13 cases). Two cases of pityriasis lichenoides were also studied. The t(2;5) translocation was not present in any of these specimens. To determine if some other somatic mutation might have resulted in inappropriate expression of ALK catalytic domain, we devised an RNA-based reverse transcriptase-PCR assay to detect transcripts encoded by this ALK region. None were found in the six additional cases of lymphomatoid papulosis that were studied. In aggregate, these results strongly suggest that inappropriate expression of ALK is not involved in the pathogenesis of these CD30+ lymphoproliferative disorders, and that lymph node-based CD30+ large cell lymphoma is a disease that is biologically distinct from skin-based CD30+ lymphoproliferative disorders and Hodgkin's disease. Using methods developed for this report, we also cloned and sequenced the t(2;5) genomic junctional sequences present in the SUP-M2 and SU-DHL-1 cell lines. These intron sequences will be useful for mapping t(2;5) breakpoint clusters.
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PMID:Lack of the t(2;5) or other mutations resulting in expression of anaplastic lymphoma kinase catalytic domain in CD30+ primary cutaneous lymphoproliferative disorders and Hodgkin's disease. 878 33

Recent studies have shown that hepatocyte growth factor (HGF) is a regulatory protein for the proliferation and differentiation of hematopoietic progenitors. The proto-oncogene c-met encodes a tyrosine kinase receptor that binds HGF. To obtain information about their possible involvement in the pathogenesis of hematopoietic tumors, we have examined the expression of HGF and c-met in a large panel of leukemia-lymphoma cell lines encompassing all major hematopoietic cell lineages. HGF and c-met mRNAs were detected by reverse transcriptase-polymerase chain reaction (RT-PCR) and Northern blotting. The panel of 92 cell lines analyzed comprised seven B-cell precursor, ten B-cell, six plasma cell, 13 T-cell, four natural killer (NK) cell, 16 myelocytic, 12 monocytic, 13 erythroid-megakaryocytic and 11 Hodgkin-anaplastic large cell lymphoma (ALCL) lines. In total 64 (70%) were RT-PCR-positive for HGF and 43 (47%) for c-met. The highest percentages of expression were found for HGF in the plasma cell (100%), NK (100%) and myeloid (75-92%) cell line categories, whereas c-met was found predominantly in plasma cell (100%) and Hodgkin-ALCL (91%) cell lines. The concomitant expression of HGF and c-met in plasma cell lines (100%) and Hodgkin-ALCL (73%) cell lines should be noted. The high HGF expression in myelocytic-monocytic cell lines (75 and 92%) contrasts with the low c-met expression (18 and 8%) in these cell lineages. In 50 cell lines, mRNA expression of these two genes was also examined at the Northern blot level: 12/50 (24%) and 4/48 (8%) were positive for HGF and c-met mRNA expression, respectively. Of note, three of the four c-met + lines belonged to the category Hodgkin-ALCL; the Hodgkin cell line SUP-HD-1 showed both HGF and c-met mRNA bands suggesting the possibility of an autocrine loop. In conclusion, we detected HGF expression in various types of leukemia-lymphoma cell lines, particularly in plasma cell and myeloid malignancies; c-met expression was found in plasma cell and Hodgkin-ALCL cell lines. Further detailed analysis of the role of this ligand-receptor pair in the pathogenesis of hematopoietic neoplasms is indicated; to this end the HGF + and c-met + cell lines described here represent exquisite model systems.
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PMID:Expression of hepatocyte growth factor and its receptor c-met in human leukemia-lymphoma cell lines. 971 11

We established a monoclonal antibody, 3G12 (IgG1), with antiproliferative effects on a human T-cell leukaemia cell line, SUP-T13. Among haematolymphoid cell lines, 3G12 reacted with most T-cell lines, Epstein-Barr transformed B-cell lines, some myelomonocytic cell lines and, most strongly with an anaplastic large cell lymphoma (ALCL) cell line, Karpas 299. The cell panel reactive with 3G12 was similar, but not identical, to that of the anti-CD30 antibody Ber-H2. 3G12 induced Fas-independent apoptosis in SUP-T13 and it also induced growth-inhibition in a limited number of other cell lines, but not Karpas 299. Immunohistochemical studies on paraffin-embedded tissue specimens demonstrated that 3G12 reacted with most CD30-positive ALCL cases and some T-cell lymphomas and some Hodgkin's lymphomas, but not with B-cell lymphomas or non-haematogeneic tumours. The immunoprecipitation study with 3G12 demonstrated a major band of 200 kD and a minor band of 100 kD, which were different from CD30. Thus 3G12 defines a novel antigen that shares a similarity to CD30 in terms of distribution among haemopoietic cells. The data suggest that the 3G12-defined antigen, designated Hal-1, is important as a marker for ALCL and may play a role in its pathogenesis.
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PMID:A monoclonal antibody, 3G12, reacts with a novel surface molecule, Hal-1, with high expression in CD30-positive anaplastic large cell lymphomas. 1044 63

One of the most peculiar immunohistological characteristics of the tumour cells of Hodgkin's lymphoma, anaplastic large cell lymphoma (ALCL), and embryonal carcinoma of the testis is the expression of the CD30 antigen. Physiologically, CD30 expression is restricted to a few activated lymphocytes in normal lymphoid tissue and a small population of decidual cells. To clarify the reasons behind this highly restricted expression pattern and to learn about the combination of transcription factors involved in this regulation in Hodgkin's lymphoma and other CD30(+) malignancies, the 5'-flanking regulatory region of the cd30 gene was analysed. The major transcription start site was determined to be 270 bases upstream of the translational start codon in the Hodgkin's lymphoma-derived cell lines L591 and L428. Reporter gene assays revealed that the CD30 promoter (-413 to 84) induces a 50- to 1000-fold higher luciferase expression in CD30(+) human lymphoid cell lines (Co, Jurkat, and the Hodgkin's lymphoma-derived cell line L540) than in CD30(-) human lymphoid cell lines (DG75, SUP-T1, and U698M), CD30(-) human carcinoma cell lines (HeLa and MCF-7), or COS1 cells. Deletion analysis defined a TATA-less, minimal promoter sequence from -164 to 84. The transcription factor Sp1 and members of the Ets family induce CD30 expression, whereas the transcription factor Sp3 diminishes its induction. These data suggest that a high Sp1/Sp3 expression ratio and a peculiar expression pattern of the Ets transcription factors are involved in the overexpression of CD30 and might contribute to the transformation of CD30(+) tumour cells.
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PMID:The restricted expression pattern of the Hodgkin's lymphoma-associated cytokine receptor CD30 is regulated by a minimal promoter. 1100 94

We recently reported deletion of the protein tyrosine phosphatase gene PTPN2 in T-cell acute lymphoblastic leukemia. Functional analyses confirmed that PTPN2 acts as classical tumor suppressor repressing the proliferation of T cells, in part through inhibition of JAK/STAT signaling. We investigated the expression of PTPN2 in leukemia as well as lymphoma cell lines. We identified bi-allelic inactivation of PTPN2 in the Hodgkin's lymphoma cell line SUP-HD1 which was associated with activation of the JAK/STAT pathway. Subsequent sequence analysis of Hodgkin's lymphoma and T-cell non-Hodgkin's lymphoma identified bi-allelic inactivation of PTPN2 in 2 out of 39 cases of peripheral T-cell lymphoma not otherwise specified, but not in Hodgkin's lymphoma. These results, together with our own data on T-cell acute lymphoblastic leukemia, demonstrate that PTPN2 is a tumor suppressor gene in T-cell malignancies.
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PMID:Mutation analysis of the tyrosine phosphatase PTPN2 in Hodgkin's lymphoma and T-cell non-Hodgkin's lymphoma. 2179 76

Classical Hodgkin lymphoma (CHL), a neoplasm of abnormal B lymphocytes (Hodgkin-Reed-Sternberg (HRS) cells), has been described to have a typical pattern of clinical presentation and dissemination often involving functionally contiguous lymph nodes. Despite the progress made in understanding CHL pathophysiology, the factors that regulate the spread of lymphoma cells in CHL are poorly understood. Sphingosine-1-phosphate (S1P), a bioactive sphingolipid present at high concentrations in the plasma and lymphatic fluid, is known to have a critical role in regulating lymphocyte trafficking mainly through sphingosine-1-phosphate receptor 1 (S1PR1). In this study, we explore the role of the S1P-S1PR1 axis in Hodgkin lymphoma cell migration and the expression of S1PR1 in CHL cell lines and clinical cases. We found that S1PR1 is present in the KM-H2 and SUP-HD1 Hodgkin lymphoma cell lines at the mRNA and protein level. In addition, functionally, S1P potently stimulated migration of both cell lines. S1P-induced migration was inhibited by the S1PR1 antagonist, VPC44116, and the S1PR1 functional antagonist, FTY720-P, but was potentiated by the S1PR2-specific antagonist, JTE013. We also determined that S1PR1 induced migration in the KM-H2 and SUP-HD1 cells via the heterotrimeric G-protein Gi and the phosphatidylinositol-3-kinase pathway. Immunohistochemical assessment of the tissue from CHL samples revealed that a subset of cases (7/57; 12%) show strong, membranous staining for S1PR1 in HRS cells. Altogether, our data indicate that S1PR1 is a functional receptor on HRS cells, which governs tumor cell migration and is expressed in a subset of CHL cases. Given the availability of S1PR1 antagonists, some of which are used clinically for modulation of the immune system, these results suggest that S1PR1 could be a future therapeutic target in the treatment of those cases of S1PR1-positive, refractory/recurrent CHL.
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PMID:Sphingosine-1-phosphate receptor 1 in classical Hodgkin lymphoma: assessment of expression and role in cell migration. 2341 11

The action of dexamethasone is initiated by, and strictly dependent upon, the interaction of the drug with its receptor followed by its translocation into the nucleus where modulates gene expression. Where the drug localizes at the intranuclear level is not yet known. We aimed to study the localization of the drug in nuclear lipid microdomains rich in sphingomyelin content that anchor active chromatin and act as platform for transcription modulation. The study was performed in non-Hodgkin's T cell human lymphoblastic lymphoma (SUP-T1 cell line). We found that when dexamethasone enters into the nucleus it localizes in nuclear lipid microdomains where influences sphingomyelin metabolism. This is followed after 24 h by a cell cycle block accompanied by the up-regulation of cyclin-dependent kinase inhibitor 1A (CDKN1A), cyclin-dependent kinase inhibitor 1B (CDKN1B), growth arrest and DNA-damage 45A (GADD45A), and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) genes and by the reduction of signal transducer and activator of transcription 3 (STAT3) and phospho signal transducer and activator of transcription 3 (phoshoSTAT3) proteins. After 48 h some cells show morphological changes characteristic of apoptosis while the number of the cells that undergo cell division and express B-cell lymphoma-2 (Bcl-2) is very low. We suggest that the integrity of nuclear lipid microdomains is important for the response to glucocorticoids of cancer cells.
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PMID:Nuclear lipid microdomain as resting place of dexamethasone to impair cell proliferation. 2536 74

The use of gentamicin for the treatment of bacterial infection has always been an interesting and highly speculated issue for the scientific community. Conversely, its effect on cancer cells has been very little investigated. We studied the effect of high doses of gentamicin on non-Hodgkin's T-cell human lymphoblastic lymphoma (SUP-T1). We showed that gentamicin delayed cell growth and induced cell death in lymphoma cells with a rather mild effect on lymphocytes. In SUP-T1 cells, GAPDH, B2M, CDKN1A and CDKN1B were down-expressed in comparison with lymphocytes. Gentamicin treatment in SUP-T1 cells restored the expression of GAPDH, B2M and CDKN1A to values similar to those of lymphocytes and caused overexpression of CDKN1B. The drug acted via sphingomyelin metabolism; in whole cells, sphingomyelinase activity was stimulated, whereas in purified nuclei, sphingomyelinase activity was inhibited and that of sphingomyelin-synthase was stimulated, with a consequent high level of nuclear sphingomyelin content. We suggest that the increase of nuclear sphingomyelin might enrich the nucleus of lipid microdomains that act as a platform for active chromatin and, thus, might be responsible for gene expression. It is possible that in lymphoblastic lymphoma, high doses of gentamicin induce a beneficial therapeutic outcome.
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PMID:Gentamicin arrests cancer cell growth: the intriguing involvement of nuclear sphingomyelin metabolism. 2562 50

Reactive oxygen species (ROS) are key modulators of apoptosis and carcinogenesis. One of the important sources of ROS is NADPH oxidases (NOXs). The isoform NOX5 is highly expressed in lymphoid tissues, but it has not been detected in any common Hodgkin or non-Hodgkin lymphoma cell lines. In diverse, nonlymphoid malignant cells NOX5 exerts an antiapoptotic effect. Apoptosis suppression is the hallmark feature of a rare type of lymphoma, termed anaplastic lymphoma kinase-positive (ALK(+)) anaplastic large-cell lymphoma (ALCL), and a major factor in the therapy resistance and relapse of ALK(+) ALCL tumors. We applied RT-PCR and Western blot analysis to detect NOX5 expression in three ALK(+) ALCL cell lines (Karpas-299, SR-786, SUP-M2). We investigated the role of NOX5 in apoptosis by small-interfering RNA (siRNA)-mediated gene silencing and chemical inhibition of NOX5 using FACS analysis and examining caspase 3 cleavage in Karpas-299 cells. We used immunohistochemistry to detect NOX5 in ALK(+) ALCL pediatric tumors. NOX5 mRNA was uniquely detected in ALK(+) ALCL cells, whereas cell lines of other lymphoma classes were devoid of NOX5. Transfection of NOX5-specific siRNA and chemical inhibition of NOX5 abrogated calcium-induced superoxide production and increased caspase 3-mediated apoptosis in Karpas-299 cells. Immunohistochemistry revealed focal NOX5 reactivity in pediatric ALK(+) ALCL tumor cells. These results indicate that NOX5-derived ROS contribute to apoptosis blockage in ALK(+) ALCL cell lines and suggest NOX5 as a potential pharmaceutical target to enhance apoptosis and thus to suppress tumor progression and prevent relapse in pediatric ALK(+) ALCL patients that resist classical therapeutic approaches.
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PMID:The NADPH oxidase NOX5 protects against apoptosis in ALK-positive anaplastic large-cell lymphoma cell lines. 2579 83


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