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)

The incidence of secondary malignancy following autologous stem cell transplantation (ASCT) is increasing. We describe a patient with stage IVB Hodgkin's disease who developed primary amelanotic malignant melanoma of the tongue 18 months following autologous stem cell transplantation. She was treated by partial glossectomy and supra-omohyoid neck dissection followed by cytokine-mediated immunotherapy. Malignant melanoma of the skin is a frequent secondary solid tumor seen in patients undergoing stem cell transplantation. However, mucosal melanoma which is rare by itself (0.2-8%) has never been reported in NHL patients following ASCT. Early diagnosis and initiation of combined local and systemic treatments including immuno-therapy may improve the outcome of this rare but lethal complication.
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PMID:Mucosal melanoma following autologous stem cell transplantation for non-Hodgkin's lymphoma (NHL). 893 60

Hodgkin's disease (HD) represents a phenotypically and genotypically heterogeneous lymphoma of CD30-positive tumour cells. Infection of the tumour cells with Epstein-Barr virus (EBV) is found in significant proportions of cases with geographical variation and represents the most common genetic abnormality detectable in HD. If present, EBV is found in all tumour cells with an usually monoclonal composition of episomes, indicating that EBV infection occurs prior to clonal expansion of the tumour cells. Largely by the EBV-encoded protein LMP1, the virus may influence the expression of differentiation antigens and apoptosis. EBV-induced modulation of cytokine expression results in the activation of autocrine and paracrine regulatory loops and may contribute to the local inhibition of EBV-specific immunity observed in EBV-positive HD.
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PMID:Epstein-Barr virus in Hodgkin's disease. 894 2

The RING-finger promyelocytic leukemia (PML) protein is the product of the PML gene that fuses with the retinoic acid receptor-alpha gene in the t(15; 17) translocation of acute promyelocytic leukemia. Wild-type PML localizes in the nucleus with a typical speckled pattern that is a consequence of the concentration of the protein within discrete subnuclear domains known as nuclear bodies. Delocalization of PML from nuclear bodies has been documented in acute promyelocytic leukemia cells and suggested to contribute to leukemogenesis. In an attempt to get new insights into the function of the wild-type PML protein and to investigate whether it displays an altered expression pattern in neoplasms other than acute promyelocytic leukemia, we stained a large number of normal and neoplastic human tissues with a new murine monoclonal antibody (PG-M3) directed against the amino-terminal region of PML. As the PG-M3 epitope is partially resistant to fixatives, only cells that overexpress PML are detected by the antibody in microwave-heated paraffin sections. Among normal tissues, PML was characteristically up-regulated in activated epithelioid histiocytes and fibroblasts in a variety of pathological conditions, columnar epithelium in small active thyroid follicles, well differentiated foamy cells in the center of sebaceous glands, and hypersecretory endometria (Arias-Stella). Interferons, the PML of which is a primary target gene, and estrogens are likely to represent some of the cytokines and/or hormones that may be involved in the up-regulation of PML under these circumstances. In keeping with this concept, we found that PML is frequently overexpressed in Hodgkin and Reed-Sternberg cells of Hodgkin's disease, a tumor of cytokine-producing cells. Among solid tumors, overexpression of PML was frequently found in carcinomas of larynx and thyroid (papillary), epithelial thymomas, and Kaposi's sarcoma, whereas carcinomas of the lung, thyroid (follicular), breast, and colon were frequently negative or weakly PML+. We did not observe any changes in the levels of PML expression as the lesion progressed from benign dysplasia to carcinoma. Our immunohistological data are consistent with the hypothesized growth suppressor function of PML and strongly suggest that PML expression levels are likely to be modulated by a variety of stimuli, including cytokines and hormones.
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PMID:Heterogeneous nuclear expression of the promyelocytic leukemia (PML) protein in normal and neoplastic human tissues. 895 36

Interleukin-10 (IL-10) has multiple effects on lymphoid development, particularly as a stimulant of activated B-cell proliferation and differentiation. It is thought that IL-10 might play a role in the development of B lymphoid malignancies based on the observation that lymphomatous tissues from HIV+ patients contain numerous cells containing IL-10 mRNA as well as IL-10 protein. The aim of this study using an Elisa test was to analyze IL-10 in the serum of 18 HIV+ patients with non Hodgkin's B lymphoma (NHL) and compared the presence of this cytokine in the serum of 18 HIV+ patients without NHL. In this comparative study we also considered the different parameters such as the mode of contamination, sex, age and number of CD4 cells. 44% of the patients with HIV-related NHL had significant levels of IL-10 (> or = 12 pg/ml) in their serum, in comparison to the patients without NHL who did not show detectable serum IL-10.
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PMID:Serum interleukin-10 in acquired immunodeficiency syndrome lymphoma patients. Seroco-Hemoco Study Group. 901 Jun 82

The incidence of non-Hodgkin's lymphoma is greatly increased in human immunodeficiency virus (HIV)-infected individuals. Most are clinically aggressive B-cell lymphomas exhibiting Burkitt-type, immunoblastic or large-cell morphology. Approximately 80% arise systemically (nodal or extranodal), and the remaining 20% arise in the central nervous system. A small proportion are body cavity-based (primary effusion) lymphomas associated with Kaposi's sarcoma-associated herpesvirus (KSHV) infection. Possible factors contributing to lymphoma development include HIV-induced immunosuppression, chronic antigenic stimulation, and cytokine overproduction. These phenomena are associated with the development of oligoclonal B-cell expansions. The appearance of malignant lymphoma is characterized by the presence of a monoclonal B-cell population displaying a variety of genetic lesions including Epstein-Barr virus (EBV) infections, c-myc gene rearrangement, bcl-6 gene rearrangement, ras gene mutations, and p53 gene mutations/deletions. The number and type of genetic lesions varies according to anatomic site of origin and histopathology. In the case of Burkitt-type lymphoma, virtually 100% exhibit c-myc gene rearrangement, two thirds display p53 gene mutations, one third contain EBV, and none exhibit bcl-6 gene rearrangements. In contrast, in the case of immunoblastic lymphoma, virtually 100% contain EBV, 25% display c-myc gene rearrangements, 20% display bcl-6 gene rearrangements, and few exhibit p53 gene mutations. These findings suggest that more than one pathogenetic mechanism is operational in the development and progression of acquired immunodeficiency syndrome (AIDS)-related lymphoma. Further work is necessary to develop a thorough understanding of the origin and pathogenesis of malignant lymphoma in the setting of HIV infection. AIDS-related lymphoma remains an important biologic model for investigating the development and progression of high-grade non-Hodgkin lymphomas as well as malignant lymphomas that develop in immune-deficient hosts.
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PMID:Molecular pathology of acquired immunodeficiency syndrome-related non-Hodgkin's lymphoma. 904 11

CD30 ligand (CD30L) is a type-II membrane glycoprotein capable of transducing signals leading to either cell death or proliferation through its specific counterstructure CD30. Although several lines of evidence indicate that CD30L plays a key role as a paracrine- or autocrine-acting surface molecule in the deregulated cytokine cascade of Hodgkin's disease, little is known regarding its distribution and biologic significance in other human hematopoietic malignancies. By analyzing tumor cells from 181 patients with RNA studies and immunostaining by the anti-CD30L monoclonal antibody M80, we were able to show that human hematopoietic malignancies of different lineage and maturation stage display a frequent and broad expression of the ligand. CD30L mRNA and surface protein were detected in 60% of acute myeloid leukemias (AMLs), 54% of B-lineage acute lymphoblastic leukemias (ALLs), and in a consistent fraction (68%) of B-cell lymphoproliferative disorders. In this latter group, hairy cell leukemia and high-grade B-cell non-Hodgkin's lymphoma (B-NHL) expressed a higher surface density of CD30L as compared with B-cell chronic lymphocytic leukemia and low-grade B-NHL. Purified plasmacells from a fraction of multiple myeloma patients also displayed CD30L mRNA and protein. A more restricted expression of CD30L was found in T-cell tumors that was mainly confined to neoplasms with an activated peripheral T-cell phenotype, such as T-cell prolymphocytic leukemia, peripheral T-NHL, and adult T-cell leukemia/lymphoma. In contrast, none of the T-lineage ALLs analyzed expressed the ligand. In AML, a high cellular density of CD30L was detected in French-American-British M3, M4, and M5 phenotypes, which are directly associated with the presence on tumor cells of certain surface structures, including the p55 interleukin-2 receptor alpha-chain, the alpha(M) (CD11b) chain of beta2 integrins, and the intercellular adhesion molecule-1 (CD54). Analysis of normal hematopoietic cells evidenced that, in addition to circulating and tonsil B cells, a fraction of bone marrow myeloid precursors, erythroblasts, and subsets of megakaryocytes also express CD30L. Finally, we have shown that native CD30L expressed on primary leukemic cells is functionally active by triggering both mitogenic and antiproliferative signals on CD30+ target cells. As opposed to CD30L, only 10 of 181 primary tumors expressed CD30 mRNA or protein, rendering therefore unlikely a CD30-CD30L autocrine loop in human hematopoietic neoplasms. Taken together, our data indicate that CD30L is widely expressed from early to late stages of human hematopoiesis and suggest a regulatory role for this molecule in the interactions of normal and malignant hematopoietic cells with CD30+ immune effectors and/or microenvironmental accessory cells.
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PMID:CD30 ligand is frequently expressed in human hematopoietic malignancies of myeloid and lymphoid origin. 905 27

Plasmids carrying the Epstein-Barr virus (EBV) latent gene EBNA1 and the EBV latent origin of replication (oriP) stay in transfected human cells as autonomously replicating extrachromosomal genetic units. They thus might represent a suitable tool for cytokine gene introduction into human tumor cells with the prospect of therapeutic antitumor vaccination. The aim of this study was to analyze whether such plasmids permit stable and efficient expression of cytokine genes in human non-Hodgkin lymphoma cells. We tested physical stability and expression levels of plasmids carrying EBNA1 and oriP for episomal maintenance, immunoglobulin light chain enhancer elements for augmentation of expression, and cytokine or marker genes after introduction into human NHL cell lines in vitro and in vivo after inoculation into nude mice. Data obtained with these EBV-based vectors were compared with another plasmid, not carrying EBNA1 and oriP. cDNAs coding for GM-CSF, IL6, TNF alpha, the chloramphenicolacetyltransferase (CAT) and the beta-galactosidase (lacZ) gene were transfected into the EBV-positive Burkitt's lymphoma cell line BL60 and the EBV-negative B cell lymphoma cell line BJA-B. EBV-derived vectors permitted a high, host cell independent transfection efficiency and high and host cell independent levels of expression. After removal of the selection pressure (hygromycin B) cytokine expression could be detected for several weeks in vitro and in vivo but, however, declined continuously. These experiments suggest that episomal BC-derived vectors represent an effective tool for cytokine gene transfer in human lymphoma cells.
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PMID:Suitability of Epstein-Barr virus-based episomal vectors for expression of cytokine genes in human lymphoma cells. 908 10

Interleukin-3 (IL-3) is a multipotent hematopoietic growth factor, which exhibits stimulatory effects on leucocytes, reticulocytes and platelets. Due to its pronounced induction of megakaryopoiesis, IL-3 is thought to be a cytokine with the potential to prevent and to overcome chemotherapy-induced thrombocytopenia. We report on four cases (two of metastatic breast cancer, one of metastatic ovarian cancer and one of Hodgkin's disease) with prolonged chemotherapy-induced thrombocytopenia in whom rhIL-3 in combination with either recombinant human (rh) granulocyte macrophage colony stimulating factor (GM-CSF) or rh granulocyte colony stimulating factor (G-CSF) was administered. In all cases, a steady and clinically significant increase in platelet counts could be observed. No major side effects, neither due to the application of rhIL-3 nor due to rhGM-CSF or rhG-CSF, occurred; only flu-like symptoms were seen, which could effectively be treated with paracetamol. This report highlights the efficacy of combined treatment with rhIL-3 plus rhGM-CSF or rhG-CSF in chemotherapy-induced thrombocytopenia, where megakaryopoiesis could be stimulated efficiently by rhIL-3. Based on this experience, the authors conclude that established thrombocytopenia as a major side effect of myelosuppressive chemotherapy should be considered as an indication for the use of rhIL-3 in interventional treatment. Further investigations in this area are encouraged.
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PMID:Treatment of prolonged chemotherapy induced severe thrombocytopenia with recombinant human interleukin-3--a report on four cases. 909 35

We investigated the potential of ten cytokines (IL2, IL3, IL4, IL6, IL10, IL13, G-CSF, GM-CSF, interferon alpha, interferon gamma) and all-trans-retinoic acid to modulate the spontaneous proliferative response in vitro of purified B-non Hodgkin's lymphoma cells of various histological subtypes. 19 malignant lymph nodes were studied. In each case the growth could be influenced by several of these modulators. Cytokines most often implicated were interferon gamma (14/19 cases, 73.7%), IL4 (13/19 cases, 68.4%), interferon alpha (12/19 cases, 63.1%). IL2 (9/19 cases, 47.3%), IL6, IL10, IL13 and ATRA were less frequently involved (6/19 cases, 31.6%) and hematopoietic growth factors (IL3, GM-CSF, G-CSF) were rarely implicated (2/19 cases, 10.5%). The values of growth stimulation ranged from a 1.1-fold to a 6.1-fold increase, and the values of growth inhibition ranged from 15% to 98%. Each cytokine could be either inhibitory or stimulatory depending on the sample analyzed, and no relationship could be found with the histological subtype. Two notable exceptions were IL2, displaying exclusively a positive effect, and ATRA displaying exclusively a negative effect. Overall, these results may have strong implications for future clinical studies using cytokines in the treatment of lymphomas. Ideally, the pattern of in vitro growth response to cytokines or ATRA should be determined individually before undertaking any cytokine treatment.
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PMID:Growth modulation of freshly isolated non-Hodgkin's B-lymphoma cells induced by various cytokines and all-trans-retinoic-acid. 913 Jun 25

The product of the protooncogene c-kit is the receptor for the hematopoietic cytokine stem cell factor (SCF). C-kit is expressed on leukemic cells of the erythroid, myeloid, and mast-cell lineage and SCF has a proliferative effect on some of these cells. The role of SCF and c-kit in lymphoid malignancies is much less clear. Here we review the role of c-kit in normal lymphopoiesis and summarize its role in lymphoid malignancies. C-kit is expressed in normal lymphopoiesis and its ligand SCF synergizes with IL-7 to enhance the proliferation of B- and T-cell progenitors. In malignant lymphopoiesis, c-kit can also be expressed in B and T-lymphoblastic cells from children with non Hodgkin's lymphoma (NHL) or acute lymphoblastic leukemia (ALL) when analyzed by the highly sensitive reverse transcriptase polymerase chain reaction (RT-PCR). While c-kit receptors were detected by flow cytometric (FCM) analysis on about 40% of fresh T-lymphoblastic biopsy tumor cell preparations or T-lymphoblastic cell lines, no receptors were detected on B-lymphoblastic fresh cells or cell lines from children with B-ALL or Burkitt's lymphoma (BL). Almost all of the lymphoblastic cells expressing c-kit protein responded to recombinant human (rh)SCF with a downregulation of c-kit receptors. A proliferative response was detected only in a minority of these cells. B-ALL or BL cell lines showed no response to rhSCF. Upregulation of c-kit in T-lymphoblastic cells could be demonstrated by the addition of IL-1 beta, TNF-alpha, TGF-beta or A23187, and downregulation by rhSCF or phorbol myristate acetate (PMA). Despite upregulation of c-kit mRNA, protein remained undetectable on B-ALL or BL cells in the presence of A23187. The metabolic state of the cells seemed to influence c-kit expression, since c-kit was upregulated in T-lymphoblastic cells by the addition of new medium. C-kit appears to play a role in the growth of some malignant T-lymphoblastic but not B-lymphoblastic cells.
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PMID:C-kit receptors in childhood malignant lymphoblastic cells. 916 31


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