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)

Matrix metalloproteinases (MMPs) and their inhibitors (tissue inhibitors of metalloproteinases, TIMPs) play essential roles in the remodelling of the extracellular matrix (ECM). Results of in vivo and in vitro studies suggest that the balance between MMPs and TIMPs is altered in neoplasia, contributing to the invasive and metastatic properties of malignant tumours. In this study we have analysed the expression of five MMP genes and TIMP-1 and TIMP-2 in 37 benign and malignant lesions of human breast using Northern blot analysis. MMP-9 (92 kDa gelatinase) and MMP-11 (stromelysin 3) were most consistently expressed by carcinomas. Based on detection of either MMP-9 or MMP-11 mRNAs, we were able to distinguish between malignant and benign disease with a predictive accuracy of 90% with 94% sensitivity and 85% specificity. Subsequently, these results were compared with results for carcinomas of colon and lung and malignant non-Hodgkin's lymphomas (NHL). Elevated MMP-9 and TIMP-1 expression was observed in all four systems. MMP-11 characterised all carcinomas as well as carcinomas in situ but was not detectable in NHL. Our data therefore argue that there are remarkably similar patterns of specific functions involved in ECM remodelling that correlate with malignancy in different human tumours of different histogenesis. However, MMP-11 expression is a characteristic of tumours of epithelial origin that is not found in lymphoid neoplasia. Thus it suggests that MMP-11 may play a regulatory role in the invasion and metastasis of carcinomas.
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PMID:Comparative analysis of the expression patterns of metalloproteinases and their inhibitors in breast neoplasia, sporadic colorectal neoplasia, pulmonary carcinomas and malignant non-Hodgkin's lymphomas in humans. 864 87

This study was conducted to assess the net proteolytic activity of human non-Hodgkin's lymphomas (NHLs). We have compared the extracellular matrix (ECM)-degradative abilities of human NHLs, reactive lymphoid hyperplasias, and established lymphoid cell lines using Matrigel invasion and elastin degradation assays. The inhibition studies allowed identification of the classes of proteinases involved in ECM degradation. Our results indicate that lymphocytes and other leukocytes derived from both human NHLs and reactive lymphoid hyperplasias are capable of Matrigel penetration, but only cells derived from the high-grade human NHLs degrade elastin in vitro. Established lymphoid cell lines (both malignant and Epstein-Barr virus immortalized) do not produce MMP-9, do not penetrate the Matrigel, and do not degrade elastin. Moreover, in human NHLs, elastolytic activity is blocked by metalloproteinase inhibitors, while inhibitors of the other classes of proteolytic enzymes have only minor effects. This study identifies metalloproteinases as the most important class of proteinases involved in ECM degradation by NHLs. The previous studies suggest that, within this class, MMP-9 represents the key enzyme that plays a role in the biological aggressiveness of human NHLs.
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PMID:Proteolytic activity of human non-Hodgkin's lymphomas. 946 83

We have examined the in vitro anticancer activity of METVAN [bis(4,7-dimethyl-1,10 phenanthroline) sulfatooxovanadium(IV); VO(SO(4))(Me(2)-Phen)(2)] against acute lymphoblastic leukemia (ALL; NALM-6 and MOLT-3), acute myeloid leukemia (AML; HL-60), Hodgkin's disease (HS445), and multiple myeloma (ARH-77, U266BL, and HS-SULTAN) cell lines as well as primary leukemic cells from patients with ALL, AML, and chronic acute myeloid leukemia (CML). METVAN induced apoptosis in NALM-6, MOLT-3, and HL-60 cells in a concentration-dependent fashion with EC(50) values of 0.19 +/- 0.03 microM, 0.19 +/- 0.01 microM, and 1.1 +/- 0.2 microM, respectively. METVAN induced apoptosis at low micromolar concentrations in primary leukemic cells from patients with ALL, AML, and CML. METVAN inhibited the constitutive expression of matrix metalloproteinase (MMP)-9 protein and its gelatinolytic activity in HL-60 cells and MMP-2 as well as MMP-9 gelatinolytic activities in leukemic cells from ALL, AML, and CML patients. Furthermore, METVAN inhibited the leukemic cell adhesion to the extracellular matrix proteins laminin, type IV collagen, vitronectin, and fibronectin and the invasion through Matrigel matrix. Further preclinical development of METVAN may provide the basis for the development of more effective chemotherapy programs.
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PMID:Bis(4,7-dimethyl-1,10-phenanthroline) sulfatooxovanadium(I.V.) as a novel antileukemic agent with matrix metalloproteinase inhibitory activity. 1130 62

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

Extracellular proteases play a crucial role in the invasive behavior of normal and transformed leukocytes. Thus far, however, most of the attention has been focused on members of the family of matrix metalloproteinases. In this work, we show that lymphoma cells can express leukocyte elastase (LE) and recruit the enzyme at their surface via ICAM-1. The expression of LE by lymphoma cells was augmented significantly by stimulation with IL-6 and IL-13, both of which also induced the expression of MMP-9. Although LE and IL-13 transcripts were detected in several non-Hodgkin's lymphomas, immunohistochemical analysis of lymphoma tissues also showed that LE was strongly expressed in infiltrating leukocytes. Given the spectrum of key molecules that can be cleaved by LE and that LE and MMP-9 are involved in the invasive behavior of normal or transformed leukocytes, our results raise the hypothesis that LE plays a crucial role in the multistep processes of inflammation and lymphoma metastasis.
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PMID:Leukocyte elastase in murine and human non-Hodgkin lymphomas. 1159 Jan 95

This is the first study to describe the role of MMP-2 and MMP-9 in Hodgkin's disease. Strong MMP-2 expression correlated with a favorable prognosis, while MMP-9 expression showed a tendency toward an adverse outcome. MMP-9 expression correlated with B symptoms and decreased new vessel formation. MMP-2 expression was associated with the nodular sclerosis subtype, and its expression was most pronounced in the vicinity of sclerosis. Neither of the gelatinases nor the extent of neovascularization correlated with tumor stage, the occurrence of bulky disease, or extranodal infiltrates. Together, these findings imply that the adverse role of MMP-9 may be associated with the controlling of immunological processes but not the invasion probabilities or neovascularization of the tumor. The favorable prognostic value of MMP-2 is surprising in view of the role of MMPs in solid tumors. This, however, may be linked to the basic biological differences of hematological malignancies vs. other tumors.
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PMID:Diverse role of MMP-2 and MMP-9 in the clinicopathological behavior of Hodgkin's lymphoma. 1243 Dec 39

Matrix metalloproteinases (MMPs) are responsible for the degradation of extracellular matrix and have an important role in tumour metastases. We investigated the role of MMP-2 and MMP-9 in Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL). The serum samples of patients with HD (n = 12), NHL (n = 30) and healthy control (n = 22) were analysed for MMP-2 and MMP-9. An immunoassay method was used for the determination of MMP-2 and MMP-9 levels. No statistical significance was found between HD and NHL groups for levels of MMP-2. There were no relation between MMP-2, MMP-9 levels and clinical characteristics of patients. The mean MMP-9 levels were found to be 555.6 +/- 140 ng/ml, 446.6 +/- 53.6 ng/ml and 111.2 +/- 10.3 ng/ml in HD, NHL and control groups, respectively. Our results suggest that MMP-9 levels are substantially increased in HD and NHL when compared with controls and may probably be used for distinguishing the benign diseases from malign lymphomas.
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PMID:Prognostic value of matrix metalloproteinases (MMP-2 and MMP-9) in Hodgkin's and non-Hodgkin's lymphoma. 1505 61

This immunohistochemical study was carried out to evaluate the role of vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 and -9 (MMP-2 and MMP-9), their inhibitor (tissue inhibitor of metalloproteinase-1, TIMP-1), and microvessel density (MVD) in the clinicopathologic behavior of childhood Hodgkin's lymphoma (HL). Paraffin-embedded histologic sections from 15 children with HL were immunohistochemically stained with MMP-2, MMP-9, TIMP-1, VEGF, and CD31 antibodies to investigate the correlation between the expression of these markers and the clinicopathologic characteristics of HL. Expression of MMP-2 and VEGF in Hodgkin and Reed-Sternberg cells (HRS) was more frequent in nodular sclerosis than in other subtypes (p=0.07 and 0.08, respectively). None of the study parameters in HRS cell were associated with age, sex, disease stage, extranodal disease, and the occurrence of bulky tumor. There was a trend toward advanced stage in negative TIMP-1 staining in HRS cells (p=0.06). In reactive lymphocytes, MMP-2 expression was correlated with MVD (r=0.68, p=0.005), and MMP-9 expression was correlated with B symptoms (p=0.003). Also, low TIMP-1 expression in reactive lymphocytes was frequently found in patients with advanced stage (p=0.048). There was a positive correlation with the ratio of MMP-2 expression in reactive lymphocytes and MVD (r=0.68, p=0.005). Expression of MMP-9 in reactive lymphocytes was correlated with MVD without statistical significance (r=0.487, p=0.06). Our results suggest that, as in many solid tumors, angiogenesis and angiogenic factors may play an important role in childhood HL. Larger series of patients are needed to determine the prognostic value of angiogenesis in childhood HL.
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PMID:Immunohistochemical expression of angiogenic cytokines in childhood Hodgkin lymphoma. 1820 52

The present study was carried out to clarify the role of matrix metalloproteinase-2 and -9 (MMP-2 and MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), vascular endothelial growth factor (VEGF), and microvessel density (MVD) in the clinicopathologic behavior of childhood B-cell non-Hodgkin lymphoma (NHL). Paraffin-embedded biopsy specimens from 25 children with NHL were studied by immunohistochemically and the correlate the expression of these markers to clinicopathologic characteristics. Positive MMP-9 staining was associated with an increased prevalence of B-symptoms (p = .046). High microvessel density (MVD) showed a tendency toward an adverse outcome and it was correlated with clinical stage (p = .023). The event-free survival of high MVD patients was less than for those with low MVD, but the difference was not statistically significant (64.1% vs. 85.71% respectively, p = 0.15). The overall survival of high MVD patients was less than for those low with MVD and the difference was statistically significant (55.53% vs. 100% respectively, p = .039). Neither gelatinases nor VEGF correlated with age, sex, disease stage, the occurrence of bulky disease, or extranodal disease. The results showed that angiogenesis and angiogenic factors might have a role in development and clinical behavior of childhood NHL. Larger series of patients are needed to determine the prognostic value of angiogenesis in childhood non-Hodgkin lymphoma.
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PMID:Role of gelatinases (MMP-2 and MMP-9), TIMP-1, vascular endothelial growth factor (VEGF), and microvessel density on the clinicopathological behavior of childhood non-Hodgkin lymphoma. 1823 55

Bone marrow angiogenesis is increased in non-Hodgkin lymphomas (NHL). Compounds affecting extracellular matrix (ECM) may modify angiogenesis. Here we investigated ECM regulators in 48 unselected NHL patients compared with 35 controls. Untreated patients had elevated (P < 0.05) serum matrix metalloproteinase (MMP) 9 and tissue inhibitor of metalloproteinase (TIMP) 1, while MMP-2, TIMP-2 and syndecan-1 were not significantly different from controls. MMP-9 mRNA was significantly up-regulated in blood mononuclear cells, while mRNA expressions of the other ECM regulators were unaltered. We found strong correlations between mRNA expressions of both vascular endothelial growth factor and fibroblast growth factor 2, and MMP-9, TIMP-1 and TIMP-2. After therapy, serum MMP-2 increased while MMP-9 decreased (P < 0.05), the others being unchanged. Several compounds affecting ECM may be involved in angiogenic activity in NHL.
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PMID:Alterations in regulators of the extracellular matrix in non-Hodgkin lymphomas. 1937


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