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)

We showed previously that human malignant non-Hodgkin's lymphomas (NHL) degrade extracellular matrix (ECM) components through the action of metalloproteinases and that elevated expression of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) correlated with a poor clinical outcome in patients with NHL. In the present study we sought to investigate whether there is any correlation between the expression of gelatinases (MMP-2 and MMP-9), TIMP-1, and the expression of cytokines and growth factors such as interleukin-1beta (IL-1beta), IL-6, IL-10, tumor necrosis factor alpha (TNF-alpha), transforming growth factor beta (TGFbeta), and basic fibroblast growth factor (bFGF) in human NHL. In lymphoma tissues obtained from 32 patients, elevated expression of IL-6 correlated significantly with elevated messenger RNA (mRNA) levels of MMP-9, MMP-2, and TIMP-1. Moreover, in human lymphoid cell lines of B- and T-cell origin (Raji, Jurkat, and NC-37), IL-6 stimulated production of MMP-9 and MMP-2 but not TIMP-1. In the Matrigel invasion assay IL-6 significantly upregulated transmigration of Raji and Jurkat cells, which in turn was inhibited by recombinant human TIMP-1 and anti-MMP-9 and MMP-2 antibodies. We postulate that IL-6 may play a role in the clinical aggressiveness of human NHL by stimulating MMP production.
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PMID:Interleukin-6 regulation of matrix metalloproteinase (MMP-2 and MMP-9) and tissue inhibitor of metalloproteinase (TIMP-1) expression in malignant non-Hodgkin's lymphomas. 1047 38

The expression of five cellular adhesion molecules (CAMs), CD54, CD58, CD11a, CD29 and CD49d, was studied in 113 B cell non-Hodgkin's lymphomas (NHL) and in normal B cells from 12 control lymph nodes. Rather than reporting the percentage of positive cells, which does not discriminate between NHL subtypes, we quantified the intensity of CAM expression using flow cytometry. Apart from CD49d the expression of all these CAMs was statistically different among the NHL subtypes as defined by the REAL classification. Low grade NHL-small lymphocytic, follicular and mantle cell lymphoma--which are derived from quiescent cells and show an indolent disease course, expressed low levels of CAMs. Conversely, high grade NHL-diffuse large cell lymphoma--which are derived from proliferating cells and are clinically aggressive, expressed high levels of CAMs. These results indicate that in malignant NHL B cell tumour growth and clinical aggressiveness may be related to the adhesive capacities of the tumour cells.
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PMID:Quantification of cellular adhesion molecules on malignant B cells from non-Hodgkin's lymphoma. 1048 95

Regulated lymphocyte trafficking is essential for the control and integration of systemic immune responses. This homing process disperses the immunologic repertoire, guides lymphocyte subsets to the specialized microenvironments that control their differentiation and survival, and targets immune effector cells to sites of antigenic insult. This review discusses data indicating that the adhesion receptors regulating the trafficking of normal lymphocytes are also expressed and functionally active in their malignant counterparts, the non-Hodgkin lymphomas. These "homing receptors" appear to mediate the highly tissue-specific dissemination of specific lymphoma subtypes, such as lymphomas of the mucosa-associated lymphoid tissues and lymphomas of the skin. Furthermore, as a result of their capability to enhance lymphoma dissemination and to transduce signals into the cell, promoting cell growth and survival, adhesion receptors may contribute to lymphoma aggressiveness. Taken together, the data offer a framework for understanding the dissemination routes of non-Hodgkin lymphomas and suggest that adhesion receptors, specifically those of the CD44 family, may present useful tools to predict prognosis in patients with lymphomas. (Blood. 2000;95:1900-1910)
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PMID:Cell adhesion receptors in lymphoma dissemination. 1070 53

Malignant Non-Hodgkin's lymphomas of the mucosa-associated lymphoid tissue display unique morphological and biological features. Unlike the situation in nodal lymphomas, they almost invariably arise from defined and recognisable precursor lesions, such as chronic infections or autoimmune diseases. From the diagnostic point of view, efforts have been undertaken to define (1) the minimal requirements for the unequivocal diagnosis of MALT-type lymphoma, (2) the regression stages after Helicobacter pylori eradication, and (3) to establish a grading system for the respective lesions. Of importance, it must be emphasized that in most cases the biopsy received in first-line is not enough in establishing a correct diagnosis with regard to biological and therapeutic implications. In particular, the accurate estimation of the biological aggressiveness of the tumour will in most cases require extensive rebiopsies. As in nodal tumours, the genetic constitution of low grade MALT-type lymphomas is more and more revealed. While data on the importance of numerical aberrations are conflicting, certain structural aberrations, such as the t(1;14) and the t(11;18), have been unequivocally linked to MALT-type lymphomas. Preliminary data suggest that these aberrations may target the apoptotic pathway. Their recognition may herald the evolution of new tumour features, such as independence from outer regulatory influences, obviously in early stages determined by the microenvironment and might be closely related to the site of tumour development and hence be a feature of the primary inflammatory disorder.
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PMID:[MALT-type non-Hodgkin's lymphoma: advances in biopsy diagnosis and pathogenesis]. 1071 98

It is generally accepted that phosphorylation plays a pivotal role in the cellular response of cell differentiation and proliferation. Immunohistochemical expression of classical protein kinase C (cPKC) subspecies (alpha, beta and gamma) in eight reactive lymphoid tissues, three normal spleens and 149 non-Hodgkin's lymphomas was examined. cPKC beta was observed primarily in the mantle zone B cells, but appeared as very faint staining in Ki-67 positive proliferated B cells in the germinal centers of secondary lymph follicles. In contrast to the reactive state, high levels of cPKC subspecies were recognized in the majority of 149 cases of non-Hodgkin's lymphoma, including those thought to have arisen from germinal center cells such as follicular lymphoma. The expression of cPKC alpha was found in higher frequency in T cell lymphomas than B cell lymphomas (P < 0.01) by the Chi-squared test. High levels of cPKC alpha were present only in high grade or highly aggressive lymphomas, showing the highest incidence in the small non-cleaved cell type, according to the International Working Formulation and National Cancer Institute (P < 0.01). cPKC gamma was not detected in normal lymphoid cells and was expressed in only four cases of non-Hodgkin's lymphomas. It is presumed that cPKC alpha and beta have a relationship to cell activation and proliferation of lymphoid cells of reactive and neoplastic states. It might be considered that the expression of cPKC alpha may have a relationship with aggressiveness in non-Hodgkin's lymphomas.
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PMID:Expression of classical protein kinase C subspecies in non-neoplastic lymphocytes and non-Hodgkin's lymphomas: an immunohistochemical study. 1084 63

AIDS-related non-Hodgkin lymphomas (AIDS-NHL) consistently derive from B-cells and are characterized by extreme clinical aggressiveness. At histological level, AIDS-NHL are classified as AIDS-related Burkitt's lymphoma (AIDS-BL), AIDS-related diffuse large cell lymphoma (AIDS-DLCL) and AIDS-related primary effusion lymphoma (AIDS-PEL). The role of cytokines in the pathogenesis and management of AIDS-NHL has been studied to a certain extent. Production of large quantities of human IL-10 occurs frequently in AIDS-BL and correlates with latent EBV infection of the tumor clone. Lesser amounts of the cytokine are released in EBV negative cases. The pathogenetic role of IL-10 in AIDS-BL is suggested by the observation that IL-10 antisense oligonucleotides inhibit proliferation of the lymphoma. A significant fraction of AIDS-BL cell lines produce TNFbeta. Among AIDS-NHL, the release of TNFbeta appears to be specific for AIDS-BL. The pathogenetic relevance of TNFbeta in lymphomagenesis is suggested by the observation that some BL cell lines use TNFbeta as an autocrine growth factor. Some cases of AIDS-BL, particularly those carrying EBV infection, also secrete IL-6, IL-7 and IL-12. With respect to AIDS-DLCL, many cases express the IL-6R, rendering these cells responsive to the paracrine stimulation by the IL-6 produced by nearby T-cells, macrophages and endothelial cells which are frequently abundant in these tumor samples. The tumor clone itself, however, generally fails to release IL-6. AIDS-PEL is characterized by secretion of large amounts of IL-6 and IL-10. Some PEL cases also release oncostatin M. Apart from human IL-6, PEL also express viral IL-6, which is encoded by the HHV-8 genome. The biological relevance of both IL-6 and IL-10 in PEL proliferation and growth has been recently clarified in vitro and in vivo. Overall, these data suggest that activation of different cytokine loops clusters with different clinico-pathologic categories of AIDS-NHL and may represent the potential target of novel therapeutic strategies.
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PMID:The role of cytokines in the pathogenesis and management of AIDS-related lymphomas. 1095 68

Human malignant non-Hodgkin's lymphomas (NHL) represent a heterogeneous group of neoplasms, which vary in their clinical behavior and pathophysiology. Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) have been shown to play a role in the pathophysiology and clinical aggressiveness of human NHL. In this setting, MMP-9 and TIMP-1 appear to be the most important members of the MMP and TIMP families, and overexpression of both correlates with a poor clinical outcome of patients with NHL. MMP-9 and TIMP-1, however, act through different mechanisms and are produced by different cell types. Expression of both is upregulated by interleukin-6 (IL-6), a cytokine that is known as one of the factors involved in the pathophysiology of human NHL. In this review we summarize the complex regulation of MMP and TIMP expression in human NHL and propose a mechanism by which MMP-9, TIMP-1 and IL-6 may influence the biology of these tumors.
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PMID:Matrix metalloproteinases and their tissue inhibitors - expression, role and regulation in human malignant non-Hodgkin's lymphomas. 1134 32

Some second malignant neoplasms are increasingly being observed following NHL and a considerable amount of data has accumulated in the literature. The authors describe a case of 65-year old male who presented with submandibular adenopathy. Results of a biopsy of the mass surgically removed revealed low grade non-Hodgkin lymphoma. During the staging workup, a meningioma and a renal cell adenocarcinoma (RCC) were unexpectedly discovered and successively resected. The patient is currently alive with no evidence of metastatic diseases 12 months after diagnosis of non-Hodgkin's lymphoma (NHL), 10 months after meningioma resection and 8 months after RCC resection. The possibility of an underlying pathologic mechanism predisposing to multiple tumours should be considered. RCC and central nervous system (CNS) neoplasms are among second malignancies with higher incidences in non-Hodgkin lymphoma patients whereas with specific regard to meningioma, one of the most common benign intracranial tumours that sometimes shows biological aggressiveness and malignancy, we have currently no data in the literature. Increased risks for several malignancies occur late in the NHL follow-up period and are largely confined to patients receiving either radiation therapy or chemotherapy. On the other hand, increased risks for renal cancer have also been reported at less than one year after diagnosis of NHL and are present in all treatment subgroups (radiation therapy, chemotherapy, other-no treatment). Increased risks for CNS malignant neoplasms have also been reported at less than one year. The authors review the pathogenic significance of this case report neoplasms association in the light of the various explicative hypothesis of this concurrence. Possible immune mechanisms associated with these neoplasm are particularly pointed up.
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PMID:[Non-Hodgkin's lymphoma, renal carcinoma, and meningioma. A clinical case]. 1199 31

DNA polymerase mu (pol mu) is a novel error-prone DNA repair enzyme bearing significant structural homology with terminal deoxynucleotidyltransferase. Whereas other human error-prone DNA polymerases identified thus far show no preferential lymphoid tissue distribution, the highest levels of pol mu mRNA have been detected in peripheral lymphoid tissues, particularly germinal center B cells. Conceivably, up-regulation of the pol mu gene may be biologically significant in lymphomagenesis, especially in the development of B-cell non-Hodgkin's lymphomas (B-NHLs), because of enhanced error-prone DNA repair activities. To explore this possibility, we generated a digoxigenin-labeled riboprobe to pol mu mRNA and used the probe and in situ hybridization to examine the expression pattern of the pol mu gene in formalin-fixed, paraffin-embedded tissue sections of 37 B-NHLs. This included eight chronic lymphocytic leukemia/small lymphocytic lymphomas, six mantle cell lymphomas, seven follicular lymphomas, nine diffuse large B-cell lymphomas, three splenic marginal zone lymphomas, two Burkitt's lymphomas, and two precursor B-lymphoblastic lymphomas. We also correlated the pol mu mRNA expression levels with the tumor proliferation index, which was assessed in each case by image analysis of Ki-67 immunostained slides. Nineteen of 21 (90%) B-NHLs arising from postgerminal center B cells (follicular lymphomas, diffuse large B-cell lymphomas, splenic marginal zone lymphomas, and Burkitt's lymphomas) exhibited high expression of pol mu mRNA. In contrast, only 2 of 16 (13%) B-NHLs arising from pregerminal center B cells (chronic lymphocytic leukemia/small lymphocytic lymphomas, mantle cell lymphomas, and precursor B-lymphoblastic lymphomas) expressed significant levels of pol mu mRNA. Pol mu gene expression did not seem to correlate with the proliferation index, especially because a significant level of pol mu mRNA was not detected in either case of precursor B-lymphoblastic lymphomas. In conclusion, pol mu gene expression is highly associated with B-NHLs of postgerminal center B-cell derivation. Furthermore, the expression level is independent of the proliferation rate and thus is unrelated to the biological aggressiveness of the tumors. These findings, along with the error-prone nature of the enzyme, suggest that up-regulation of pol mu gene expression may be a contributing factor to the pathogenesis of a subset of B-NHLs through DNA repair-associated genomic instability.
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PMID:DNA polymerase mu gene expression in B-cell non-Hodgkin's lymphomas: an analysis utilizing in situ hybridization. 1236 8

The principles of the new WHO classification of haematopoietic and lymphoid tumours are based on those defined in the Revised European American classification of Lymphoid neoplasms (REAL), published by the International Lymphoma Study Group (ILSG) in 1994. Thus, the new WHO classification may be considered an updated version of the REAL classification rather than of the old WHO classification published in 1976. Disease entities are defined on the basis of morphological, phenotypic, genotypic, and clinical data. The relative impact of these characteristics varies among different diseases and there is "no gold standard". Thus, the strict hierarchy among diagnostic criteria, headed by morphology and followed by immunohistochemistry and genetics, has been discontinued. The WHO classification not only encompasses lymphoid tumours but extends to myeloid, mast cell and histiocytic/dendritic cell malignancies. Neoplasms are primarily stratified according to their tumour cell lineage. For each neoplasm a cell of origin is postulated. The classification of lymphoid malignancies recognises three major categories, B-cell neoplasms, T-/NK-cell neoplasms, and Hodgkin lymphomas. B-cell and T-cell lymphomas are further divided into precursor neoplasms and mature neoplasms, the latter being subdivided according to their clinical manifestation into disseminated/leukaemic, extranodal and nodal malignancies. In contrast to previous classifications, the neoplasms are grouped neither according to their histological grade (Kiel classification) nor according to their clinical aggressiveness (International Working Formulation). However, the histological grade is considered a prognostic factor which enters into the description of each disease entity. Hodgkin's disease, now more appropriately termed Hodgkin lymphoma, comprises nodular lymphocyte-predominant Hodgkin lymphoma and classical Hodgkin lymphomas of nodular sclerosis, mixed cellularity, lymphocyte-depleted and lymphocyte-rich subtype. For practical purposes this minireview disregards the description of myeloid, macrophage/histiocytic, dendritic cell and mast cell disorders. Furthermore, the present paper is restricted to those lymphoid tumours that are not already identically described in the REAL classification, in order to focus on what is really new in the WHO classification.
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PMID:Who is WHO and what was REAL? 1258 44


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