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 expression of hypoxia inducible factors (HIF) 1alpha and 2alpha, of vascular endothelial growth factor (VEGF) and of the phosphorylated form of its receptor VEGFR2 (pVEGFR2/KDR) were investigated immunohistochemically in a series of 146 B-cell non-Hodgkin's lymphomas and 48 normal lymph nodes. These proteins were significantly up-regulated in neoplastic lymphocytes and a significantly higher expression of HIF1alpha (p = 0.05), VEGF (p = 0.02) and pVEGFR2/KDR (p = 0.007) was recorded in diffuse large B-cell lymphomas(DLBCL) compared to follicular lymphomas (FL). A strong statistical association of pVEGFR2/KDR expression with high HIF1alpha, HIF2alpha and VEGF was noted in both DLBCL and FL. HIF1alpha andHIF2alpha were linked with VEGF expression but no association between HIF1alpha and HIF2alpha was noted. Vascular density was significantly higher in the lymphoma compared to normal tissue, but there was no association with any of the examined parameters. It is concluded that the VEGF/receptor pathway is active in more than half of NHLs and particularly in DLBCL. The intimate correlation of VEGF production with the presence of phosphorylated VEGF-receptors strongly supports the concept of an autocrine pathway. The strong association of HIFalphas with the expression of VEGF and pVEGFR2/KDR found in the study provide strong evidence on the role of HIFalphas inthe activation of angiogenic and VEGF-autocrine pathways that may be critical therapeutic targets for HIF-inhibitors or other anti-angiogenic agents.
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PMID:Phosphorylated VEGFR2/KDR receptors are widely expressed in B-cell non-Hodgkin's lymphomas and correlate with hypoxia inducible factor activation. 1846 46

Angiogenesis is a prerequisite for solid tumor growth, but there is relatively limited data regarding Hodgkin lymphoma. The purpose of this study was to examine the immunohistochemical expression of angiogenic and proliferation markers in Hodgkin biopsies in relation to clinical parameters. Immunostaining was performed on 65 Hodgkin biopsies with vascular endothelial growth factor (VEGF), hypoxia inducible factor-1 alpha (HIF-1alpha), platelet-derived growth factor receptor alpha (PDGFRalpha), Ki-67, and p53. Microvessel density (MVD) was determined by CD31 staining. In all cases, neoplastic cells and reactive background cells were evaluated. The neoplastic population expressed VEGF in 48% of the cases, HIF-1alpha in 54% of the cases, and PDGFRalpha in 95% of the cases. Both Ki-67 and p53 were positive in neoplastic cells in over 60% of the cases. The MVD had a median of 2.6/0.0625mm(2) which was not different from normal lymph nodes. VEGF in the non-neoplastic compartment showed increased staining in Ann Arbor stage I-II versus III-IV. In conclusion, VEGF, HIF-1alpha, and predominantly PDGFRalpha are expressed in neoplastic cells in the majority of Hodgkin lymphomas. As microvessel formation is not increased in Hodgkin, additional functions of these angiogenic molecules should be investigated.
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PMID:Histological expression of angiogenic factors: VEGF, PDGFRalpha, and HIF-1alpha in Hodgkin lymphoma. 1895 Sep 58

The expression of lactate dehydrogenase 5 (LDH5), the major LDH isoenzyme sustaining the anaerobic transformation glycolysis was examined in B-cell non-Hodgkin lymphomas. Multi-tissue slides obtained from patients with diffuse large B-cell lymphomas (DLBCL; 95 cases), follicular lymphomas (FL; 49 cases) and from non-neoplastic lymph nodes (48 cases) were used for immuhistochemical analysis. High LDH5 expression (cytoplasmic and nuclear) was noted in 79/95 and 29/49 cases of DLBCL and FL, respectively (p = 0.002). No expression was noted in non-neoplastic lymphocytes. In DLBCL, LDH5 expression was significantly related to hypoxia inducible factor HIF1alpha, HIF2alpha, vascular endothelial growth factor (VEGF) and phosphorylated vascular endothelial growth factor receptor 2 (VEGFR2/KDR) expression. In FL, however, a significant relation was confirmed with pVEGFR2/KDR and HIF2alpha. FL cases with the highest microvessel density were those, which lacked both LDH5 and VEGF expression. It is concluded that LDH5 is highly upregulated in B-cell non-Hodgkin lymphomas and is in direct relation to HIFs expression. LDH5 expression is linked with activated VEGFR2/KDR expression in both lymphoid lesions.
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PMID:Lactate dehydrogenase 5 expression in non-Hodgkin B-cell lymphomas is associated with hypoxia regulated proteins. 1902 Oct 62

Angioimmunoblastic T-cell lymphoma (AILT) is a malignant disease of peripheral T-cell origin that is characterized by a prominent proliferation of high endothelial venules in the lymph node. To investigate angiogenic mechanisms in AILT we measured the angiogenic mediator gene expression levels in the lymph nodes of 54 non-Hodgkin lymphoma patients, by immunostaining and quantitative reverse transcription polymerase chain reaction. Angiogenic mediators angiopoietin (Ang) 1 (ANGPT1), Ang2 (ANGPT2) and their receptor, Tie2 (TEK), vascular endothelial growth factor (VEGF; VEGFA) and its receptor, VEGFR2 (KDR), and hepatocyte growth factor (HGF) and its receptor, c-Met (MET) were all more highly expressed in AILT lymph nodes (16 cases) than in B-cell lymphomas (24 cases). Moreover, significantly higher Ang1 and Tie2 expression was detected in AILT cases with CD10-positive neoplastic T-cells by comparison with unspecified peripheral T-cell lymphoma (14 cases). Immunostaining confirmed the expression of Ang1 and VEGF by both neoplastic T-cells and follicular dendritic cells. These results suggest that the angiopoietin system may play an important role in the development of high vascularity in AILT lymph nodes. Consequently, as neoplastic T-cells and follicular dendritic cells are both increased in AILT and may represent an important source of angiogenic mediators, targeting these cells with anti-angiogenic strategies might represent a novel therapy for AILT.
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PMID:Angiogenic mediators of the angiopoietin system are highly expressed by CD10-positive lymphoma cells in angioimmunoblastic T-cell lymphoma. 1912 Mar 65

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

Angiogenic switch marks the beginning of tumor's strategy to acquire independent blood supply. In some subtypes of non-Hodgkin's lymphomas, higher local vascular endothelial growth factor (VEGF) expression correlates with increased microvessel density. However, this local VEGF expression is higher only in tumors with elevated expression of the receptors of the growth factor, suggesting an autocrine growth-promoting feedback loop. Several studies have indicated that VEGF receptors are also targeted by Tat protein from the HIV-1-infected cells. Given the similarity of the basic region of Tat to the angiogenic factors (basic fibroblast growth factor, VEGF), Tat mimics these proteins and binds to their receptors. We evaluated the role of HIV-1 Tat in regulating the level of VEGF expression and microvessel density in the AIDS-related diffuse large B-cell (DLBCL) and Burkitt lymphomas (BL). By luciferase assay, we showed that VEGF promoter activity was downregulated in vitro in cells transfected with Tat. Reduced VEGF protein expression in primary HIV-1 positive BL and DLBCL, compared to the negative cases, supported the findings of promoter downregulation from the cell lines. Microvascular density assessed by CD34 expression was, however, higher in HIV-1 positive than in HIV-1 negative tumors. These results suggest that Tat has a wider angiogenic role, besides the regulation of VEGF expression. Thus, targeting Tat protein itself and stabilizing transient silencing of VEGF expression or use of monoclonal antibodies against their receptors in the AIDS-associated tumors will open a window for future explorable pathways in the management of angiogenic phenotypes in the AIDS-associated non-Hodgkin's lymphomas.
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PMID:HIV-1 Tat mimetic of VEGF correlates with increased microvessels density in AIDS-related diffuse large B-cell and Burkitt lymphomas. 1966 99

Intussusceptive microvascular growth (IMG), which occurs by splitting of the existing vasculature by transluminal pillars or transendothelial bridges, has been demonstrated in several tumors such as colon and mammary carcinomas, melanoma and B-cell non-Hodgkin's lymphomas. In this study, we have correlated in human glioma the extent of angiogenesis, evaluated as microvascular density, the immunoreactivity of tumor cells to vascular endothelial growth factor (VEGF), vessel diameter and IMG to the tumor stage. Results demonstrate for the first time a relationship in human glioma progression between angiogenesis, VEGF immunoreactivity of tumor cells, vessel diameter and the number of connections of intraluminal tissue folds with the opposite vascular wall, expression of IMG and suggest that IMG could be a mechanism of compensatory vascular growth occurring in human glioma. The advantages are that (1) blood vessels are generated more rapidly; (2) it is energetically and metabolically more economic; (3) the capillaries thereby formed are less leaky.
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PMID:Intussusceptive microvascular growth in human glioma. 1988 13

Published data strongly suggest that tumor progression and malignancy are associated with increased angiogenesis. However, no data have been published concerning the relationship between microvascular density (MVD), tumor cytosol, and blood vascular endothelial growth factor (VEGF) concentrations in canine non-Hodgkin lymphoma (C-NHL), a neoplasm that shares biological and clinical characteristics with human NHL. We have evaluated MVD and tumor cytosol, serum (S), platelet-poor plasma (P-PP), plasma-activated platelet rich (P-APR) VEGF concentration in a series of 63 B-cells C-NHL by means of immunohistochemistry and enzyme-linked immuno-sorbent assay (ELISA) detection of VEGF. We found that MVD, VEGF from cytosol, and VEGF from P-APR are significantly correlated (p ranging from 0.001 to 0.003) and that these parameters paralleled with the malignancy degree of NHL. Accordingly, spontaneous C-NHL seems to be an interesting model to study the role of angiogenesis as interspecies pathway of tumor malignancy and we suggest that VEGF from P-APR might be a novel useful circulating bio-marker of tumor angiogenesis.
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PMID:Vascular endothelial growth factor concentrations from platelets correlate with tumor angiogenesis and grading in a spontaneous canine non-Hodgkin lymphoma model. 2000 Dec 31

Increased levels of circulating VEGF-A have been demonstrated in patients with non-Hodgkin lymphoma (NHL) and are associated with progressive disease and poor clinical outcome. We investigated the role of VEGF-A in lymphoma tumour growth on a molecular level in order to identify the mechanism of VEGF-A-promoted tumour growth and to identify the potential targets for therapy. We used a model in which Daudi (human Burkitt lymphoma) tumour cells were transduced with VEGF-A165 or an empty vector (negative control) and subcutaneously injected in NOD/SCID mice. The weight of tumours overexpressing VEGF-A was increased 4-fold compared to that of control tumours (p<0.0001), whereas no in vitro growth advantage was demonstrated upon VEGF-A overexpression. VEGF-A-tumours were associated with increased microvessel densities (p=0.004) and increased tumour cell proliferation (Ki67; p<0.001) compared to control tumours. VEGF-A-tumours were characterised by upregulation of phosphorylated STAT-4 and STAT-6 and downregulation of phospho-p27(KIP1), a crucial cell cycle inhibitor (p<0.05). This was accompanied by increased levels of phosphorylated receptor tyrosine kinases, including EGFR (ErbB-2 and ErbB-4, p<0.05), an upstream regulator of STAT proteins. We demonstrated that various mouse-derived cytokines produced by mouse-derived tumour stromal cells are upregulated in VEGF-A-tumours compared to control tumours (p<0.05). These results indicate an important role for the tumour microenvironment in paracrine promotion of lymphoma tumour growth in response to tumour-derived VEGF-A. In conclusion, lymphoma-derived VEGF-A promoted lymphoma tumour growth in a paracrine loop by activation of tumour stromal cells. Our study reveals VEGF-A and STAT proteins as potential additional targets in the treatment of lymphoma.
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PMID:VEGF-A promotes lymphoma tumour growth by activation of STAT proteins and inhibition of p27(KIP1) via paracrine mechanisms. 2006 7

Intravascular large B-cell lymphoma (IVLBCL) is a rare, aggressive and often fatal non-Hodgkin lymphoma characterized by preferential growth of malignant B-cells within the lumina of small vessels. Rituximab plus anthracycline-based chemotherapy is the current standard regimen for IVLBCL, however it has minimal efficacy in relapsed or refractory diseases. Recent clinical trials have shown a significant anti-lymphoma activity of mammalian target of rapamycin (mTOR) inhibitors in relapsed and refractory diffuse large B-cell lymphoma (DLBCL); however, the activation status of the mTOR pathway and the therapeutic potential of mTOR inhibitors in IVLBCL have not yet been studied. Here we described the clinicopathological features of 3 cases of IVLBCL diagnosed at our institutions, and evaluated the activation status of the mTOR signaling in these tumors. Our results showed that the mTOR complex 2 pathway was selectively upregulated in IVLBCL, as evidenced by a predominant nuclear localization of the activated form of mTOR (p-mTOR at Ser2448) with concomitant overexpression of nuclear p-Akt (Ser473) and vascular endothelial growth factor (VEGF)-A in the lymphoma cells. These data suggest that overactivation of mTOR pathway may play a role in lymphomagenesis of IVLBCL and mTORC2 inhibitors may be beneficial in treating IVLBCL.
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PMID:Intravascular large B-cell lymphoma: report of three cases and analysis of the mTOR pathway. 2213 26


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