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)

Vascular endothelial growth factor (VEGF) is one of the main angiogenic cytokines in human solid tumours and inhibition of VEGF-induced angiogenesis suppresses tumour growth. Some groups of malignant lymphoma, including peripheral T-cell lymphomas and Hodgkin's disease, are characterized by a conspicuous proliferation of small vessels. To test the hypothesis that VEGF may also be involved in the angiogenesis in lymphomas and other lesions of the lymphoid system, VEGF expression was analysed in tissues, employing in situ hybridization with a 35S-labelled RNA probe specific for this cytokine. Significant expression of VEGF transcripts was observed in Hodgkin's disease and peripheral T-cell lymphomas, particularly of the angioimmunoblastic type. In contrast, expression of this cytokine was minimal or absent in follicle centre lymphoma and chronic lymphocytic leukemia of B-cell type. VEGF was mainly observed in reactive non-lymphoid CD68-negative cells, which probably represent fibroblasts or myofibroblasts. In normal and ulcerated tonsils, VEGF was expressed in the squamous epithelium but only rarely found in the lymphoid tissue. Although infectious mononucleosis tonsils contained high numbers of VEGF-positive cells in the interfollicular zone, expression of this cytokine was not found in Epstein-Barr virus (EBV)-infected cells, as determined by simultaneous in situ hybridization for VEGF and EBV-encoded small nuclear RNAs (EBER). In 5/8 cases of Castleman's disease, germinal centres containing small vessels also showed expression of VEGF, in contrast to normal tonsillar germinal centres which are devoid of both vessels and VEGF transcripts. It is concluded that VEGF may be involved in the induction of the angiogenesis of both peripheral T-cell lymphomas and Hodgkin's disease, but not in low-grade B-cell lymphomas. In contradistinction to solid tumours, in which this cytokine is commonly secreted by the tumour cells themselves, in malignant lymphoma VEGF is not a product of neoplastic cells. Vascularization of germinal centres in Castleman's disease may also be a consequence of abnormal local expression of VEGF.
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PMID:Expression of vascular endothelial growth factor in lymphomas and Castleman's disease. 937 Sep 46

Angiogenesis is an important component in the progression and metastasis of solid tumors. We now appreciate that angiogenesis is also critically involved in the pathogenesis of hematologic malignancies. Current data suggest important prognostic and therapeutic implications of angiogenesis in a variety of malignancies of the hematopoietic system, including acute and chronic leukemias, myeloproliferative diseases, multiple myeloma, non-Hodgkin's lymphomas, and Hodgkin's disease. Vascular endothelial growth factor (VEGF) is a major angiogenic factor that regulates multiple endothelial cell functions, including mitogenesis. Cellular and circulating levels of VEGF are elevated in hematologic malignancies and are adversely associated with prognosis. Angiogenesis is a very complex, tightly regulated, multistep process, the targeting of which may well prove useful in the creation of novel therapeutic agents. Current approaches being investigated include the inhibition of angiogenesis stimulants (e.g., VEGF), or their receptors, blockade of endothelial cell activation, inhibition of matrix metalloproteinases, and inhibition of tumor vasculature. Preclinical, phase I, and phase II studies of both monoclonal antibodies to VEGF and blockers of the VEGF receptor tyrosine kinase pathway indicate that these agents are safe and offer potential clinical utility in patients with hematologic malignancies.
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PMID:The vascular endothelial growth factor (VEGF) signaling pathway: a therapeutic target in patients with hematologic malignancies. 1170 Mar 90

Vascular endothelial growth factor (VEGF) is involved in tumour angiogenesis, an important process for the growth and metastatic potential of solid tumours. Numerous studies have demonstrated up-regulation of VEGF at both mRNA and protein level in various tumours and a correlation with advanced stage and prognosis has been demonstrated in some cases. Limited information exists about its role in lymphoid malignancies and in particular, Hodgkin's disease. The present study examined the immunohistochemical expression of VEGF using the monoclonal antibody VG1 in a series of 61 cases of Hodgkin's disease, including both classical Hodgkin's disease and the nodular lymphocyte predominance variant, and correlated these results with microvessel density, using an anti-CD31 monoclonal antibody. In 41 cases (70.6%) of classical Hodgkin's disease and one of the three cases of nodular lymphocyte predominance Hodgkin's disease, the neoplastic Reed-Sternberg and Hodgkin cells expressed VEGF. The staining observed was cytoplasmic, either diffuse or with a focal paranuclear distribution. Macrophages were always positive, while reactive lymphocytes showed occasional positivity. A variable amount of strong extracellular staining was also observed in the tissue stroma and intravascular plasma staining was prominent. There was no statistically significant relationship between VEGF expression and the subtype of Hodgkin's disease or microvessel density. In vitro studies using the Reed-Sternberg cell lines L428 and KM-H2 were also performed in both normoxia and hypoxia and VEGF protein production was assessed by flow cytometry (FACS), immunoassay of cell culture supernatant, and RT-PCR. Analysis by FACS demonstrated a subset of cells in both cell lines reacting with VG1 and analysis of secreted VEGF (pg/ml per 1x10(6) cells) in cell culture supernatant confirmed the normoxic production in both cell lines and significant hypoxic induction (p<0.005). Additionally, both cell lines expressed VEGF mRNA, as demonstrated using the RT-PCR method. In conclusion, neoplastic cells express VEGF in Hodgkin's disease, as is the case in solid tumours, and this expression may be induced by hypoxia. The presence of VEGF in reactive macrophages and in the extracellular matrix might facilitate tumour progression.
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PMID:Vascular endothelial growth factor (VEGF) is expressed by neoplastic Hodgkin-Reed-Sternberg cells in Hodgkin's disease. 1451 52

Angiogenic cytokines regulate B-cell lymphopoiesis and are related to prognosis in B-cell lymphoproliferative disorders. Transforming growth factor-beta (TGF-beta) inhibits mature B-cell proliferation and immunoglobulin production. Increased levels of serum vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are associated with poor prognosis in non-Hodgkin lymphoma (NHL). To understand the expression of angiogenic cytokines at different stages of B-cell differentiation in lymph nodes, we examined the immunohistochemical expression of TGF-beta, VEGF, bFGF, and their receptors in five patients with reactive benign lymphadenopathy and 12 patients with B-cell NHL (mantle cell lymphoma, 4; small cleaved cell follicular lymphoma, 5; lymphoplasmacytic lymphoma, 3). In benign lymph nodes, TGF-beta1, TGF-beta2, and TGFbetaRII were positive in prefollicular mantle cells, follicular center cells, and postfollicular plasma cells. Basic FGF, FGF-R1, and FGF-R4 were positive in large follicular center cells and postfollicular plasma cells. Vascular endothelial growth factor was positive in large follicular center cells and postfollicular plasma cells. In NHL, TGF-beta and its receptors were weakly positive in small cleaved cell follicular lymphoma; VEGF was strongly positive in lymphoplasmacytic lymphoma and weakly positive in mantle cell lymphoma. Basic FGF and its receptors were negative in NHL; however, FGF-R4 was positive in some cases of small cleaved cell follicular lymphoma. Our findings suggest that TGF-beta, bFGF, and their receptors have opposite roles in B-cell differentiation and maturation in benign lymph nodes. Transforming growth factor-beta and its receptors have an important role in germinal center development; loss of their activity could be associated with abnormal clonal proliferation of NHL.
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PMID:Immunohistochemical expression of angiogenic cytokines and their receptors in reactive benign lymph nodes and non-Hodgkin lymphoma. 1261 67

Vascular endothelial growth factor (VEGF), basic-fibroblast growth factor (bFGF), hepatocyte growth factor (HGF), and angiogenin are important angiogenic factors. In 65 patients with non-Hodgkin's lymphoma (NHL), pre-treatment VEGF, bFGF, and HGF levels were significantly elevated compared to normal individuals, while angiogenin levels were significantly subnormal. In 37 patients with Hodgkin's disease, pre-treatment levels of VEGF and HGF were significantly elevated, bFGF levels were normal, and angiogenin levels were significantly subnormal. In patients with NHL, post-therapy levels of angiogenin were independently predictive of survival. Both pre-therapy and post-therapy VEGF levels were independently predictive of survival in patients with HD.
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PMID:Clinical relevance of circulating angiogenic factors in patients with non-Hodgkin's lymphoma or Hodgkin's lymphoma. 1512 Sep 36

Angiogenesis plays an important role in the progression of tumors. This relationship has been described in several hematologic malignancies. Vascular endothelial growth factor and basic fibroblast growth factor are predictors of poor prognosis in leukemia and non Hodgkin's lymphoma. Bone marrow microvessels were found increased in multiple myeloma, but also in lymphoma and in acute lymphoblastic leukemia. Microvessel density is correlated with decreased survival in myeloma patients and relapse or resistance to chemotherapy in lymphoma. New drugs with antiangiogenic activity such as bevacizumab (binding and inactivation of VEGF) or VEGF-tyrosine kinase inhibitors have shown promising results in phase 1 trials. It will therefore be a future challenge to integrate anti-angiogenesis agents in currently existing treatment protocols to improve the outcome of therapy.
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PMID:[Angiogenesis and hematologic malignancy]. 1784 10

Increased angiogenesis has been shown to be a feature of non-Hodgkin lymphomas (NHL). In the current study, the pretreatment levels of circulating molecules related to angiogenesis were determined in 49 B-cell NHL patients and correlated with histological grade, disease stage and prognostic score. In 25 patients, the same molecules were defined after standard treatment. Vascular endothelial growth factor (VEGF), angiogenin, interleukin-2 (IL-2), IL-6, IL-8 and IL-16 were measured. Increased levels of VEGF, IL-6 and IL-8 were found in the whole group of untreated patients in comparison with normal controls (P < 0.05), whereas, IL-2 was higher in the subgroup of indolent NHL. Overall, there was no significant decrease in the levels of these molecules after treatment. However, by stratification into group of responders vs. non-responders pretreatment IL-8 was significantly increased whereas IL-16 was decreased in the subgroup of complete responders. According to the REAL classification IL-2 was higher in the low risk compared with intermediate plus high-risk group. There was no association with disease stage or the International Prognostic Score. Both indolent and aggressive B cell lymphomas have increased production of angiogenic mediators and cytokines with IL-8 and IL-16 potentially reflecting the response to treatment.
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PMID:Angiogenesis-related growth factors and cytokines in the serum of patients with B non-Hodgkin lymphoma; relation to clinical features and response to treatment. 1819 Apr 63

No curative treatment is currently available for refractory or relapsed Hodgkin lymphoma (HL) after high-dose chemotherapy. Thus, new drugs with different modes of action are needed. Vascular endothelial growth factor (VEGF), a key regulator of tumor-angiogenesis, is elevated in sera of patients with HL. Hodgkin and Reed-Sternberg cells also express the growth-stimulating VEGF-R2 receptor suggesting that VEGF could contribute to the pathophysiology of this malignancy. We investigated the effects of the humanized anti-VEGF monoclonal antibody bevacizumab (BV) against human HL xenografts in severe combined immune deficiency mice and in a compassionate use program in HL patients with multiple relapsed and progressive diseases. After a 4-week run-in phase of single agent BV, combined gemcitabine and BV therapy was administered. In the animal model, BV delayed the growth of HL tumors significantly (P=0.0004). Out of 5 patients included, BV alone had biologic effects as determined by tumor size, blood flow, fluorodeoxyglucose-uptake, and serum markers CCL17/thymus and activation-related chemokine, and sCD30 in 4 patients. The combination of BV and gemcitabine led to partial or complete remission in 3 of 5 patients. Accordingly, VEGF deprivation by the anti-VEGF antibody BV has antitumor activity in established HL tumors in a preclinical model. Furthermore, BV single agent therapy has biologic effects in HL patients indicating clinical activity. On the basis of these results, a prospective clinical study has been initiated to further investigate the impact of this antiangiogenic approach in HL.
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PMID:Effects of the anti-VEGF monoclonal antibody bevacizumab in a preclinical model and in patients with refractory and multiple relapsed Hodgkin lymphoma. 1960 43

Vascular endothelial growth factor (VEGF) seems to play a central role in angiogenesis-lymphangiogenesis in hematological malignancies. There are limited data related to childhood hematologic malignancies. The aim of the study was to evaluate soluble VEGF (sVEGF) levels in children with acute leukemia and malignant lymphoma (ML) at diagnosis and in remission. The levels of serum sVEGF were measured by enzyme-linked immunosorbent assay (ELISA) in 20 children with acute leukemia, 33 children with different histopathological subtypes of ML, and 20 healthy controls. The levels of sVEGF at diagnosis (range 2 -1040 pg/mL; median 52 pg/mL) was significantly lower than in remission (range 136 -1960 pg/mL; median 630 pg/mL) in acute myeloid leukemia (AML) group (P = .018). The sVEGF levels at diagnosis (range: 2 -640 pg/mL; median 89 pg/mL) was significantly lower compared to remission values (range: 116 -1960 pg/mL; median 136 pg/mL) in patients with acute lymphoblastic leukemia (ALL) (P = .002). In ML group, including Burkitt's lymphoma (BL), T-cell non-Hodgkin's lymphoma (NHL), and Hodgkin's lymphoma (HL), sVEGF levels at diagnosis were higher than remission levels, but there was no statistically significant difference (P >.05). On the other hand, there were significant difference between levels in active disease and control group, ie, BL versus control, T-cell NHL versus control, and HL versus control (P = .008, P = .043, P = .007, respectively). The authors noticed that sVEGF levels showed distinct behavioral pattern in different childhood malignancies at diagnosis and in remission. In acute leukemia and ML patients, VEGF acts through different pathophysiological mechanisms, in both bone marrow (BM) angiogenesis and lymphoid tissue lymphangiogenesis.
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PMID:Does serum soluble vascular endothelial growth factor levels have different importance in pediatric acute leukemia and malignant lymphoma patients? 2067 20

Vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2) play important roles in tumor angiogenesis. Recent reports found that COX-2 expression had prognostic value in classical Hodgkin lymphoma (cHL). The purpose of this study was to measure the expression of COX-2, B-cell lymphoma-2 (Bcl-2), VEGF, and CD31 and assess their prognostic significance and potential correlation with clinical variables in cHL. A total of 167 cHL specimens were evaluated retrospectively by immunohistochemical methods for COX-2, Bcl-2, and VEGF expression and for CD31 to measure the microvessel density (MVD). Correlations between COX-2, Bcl-2, VEGF, MVD, and clinicopathologic factors were assessed, and prognostic significance was determined. COX-2, Bcl-2, and VEGF were expressed in 27.5%, 8.3%, and 33.5% of the specimens, respectively. A positive correlation was found between COX-2 and VEGF expression (P<0.001). The MVD was significantly higher in tumors positive for both COX-2 and VEGF compared with that in tumors negative for both markers (P=0.047). COX-2 expression was associated with a lower overall survival rate (P=0.015). High MVD was associated with a lower event-free survival rate (P=0.014). COX-2 was an independent prognostic factor for overall survival on multivariate analysis (P=0.013). COX-2 and VEGF correlated with angiogenesis and tumor progression in cHL. The findings support targeting COX-2 as a potential new therapeutic approach in cHL.
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PMID:Prognostic significance of COX-2 expression and correlation with Bcl-2 and VEGF expression, microvessel density, and clinical variables in classical Hodgkin lymphoma. 2385 30


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