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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Extensive studies have identified reliable markers of lymphatic endothelial cells, and mechanisms and molecules that regulate development and growth of the lymphatic vessels. Vascular endothelial growth factors (VEGF)-C and VEGF-D, and their cognate receptor tyrosine kinase, VEGF receptor-3 (VEGFR-3), are critical regulators of lymphangiogenesis. By binding to its endothelial cell surface receptors VEGFR-1 and VEGFR-2, VEGF-A mediates vascular leakage, endothelial proliferation and migration. Angiopoietin-2 (Ang-2) is expressed at sites of blood vessel remodeling and invasion, and factors that induce angiogenesis in vivo, such as VEGF-A, upregulate Ang-2 in endothelial cells. In this review, we summarize the literature concerning the crosstalk between angiogenesis and lymphangiogenesis in tumor progression, that is, involvement of VEGF-C, VEGF-D and VEGFR-3 in angiogenesis, and the role played by VEGF-A and Ang-2 in lymphangiogenesis, respectively.
Leukemia 2004 Jun
PMID:Crosstalk between angiogenesis and lymphangiogenesis in tumor progression. 1505 48

Angiogenesis in solid tumors is important to tumor growth, invasion and metastasis. Recently, it has been suggested that angiogenesis plays a certain role in the development of hematopoietic malignancies, including leukemia and multiple myeloma. We evaluated tumor angiogenesis in the bone marrow (BM) of multiple myeloma (MM) patients by calculating microvessel density (MVD) in needle-biopsy specimens obtained from 51 cases of untreated MM or monoclonal gammopathy of undetermined significance (MGUS). The MVD in the BM of donors for transplantation and patients with non-hematological diseases was calculated as a control. There was an obvious increase in MVD in the BM of MM patients, and the MVD correlated with the grade of myeloma cell invasion of the BM in the untreated MM cases. It was recently reported that thalidomide might be effective for the treatment of MM. We assessed the effect of thalidomide on angiogenesis in BM treatment of 11 patients with refractory MM. The concentration of M-protein in the serum or urine of seven of the 11 patients was reduced by at least 30% after thalidomide treatment, and MVD in the BM decreased in three of these seven cases in response to thalidomide. Increased plasma concentrations of basic fibroblast growth factor (FGF-2) and vascular endothelial growth factor (VEGF) were observed in all 11 cases before thalidomide administration and both levels were reduced after treatment with thalidomide. Augmented angiogenesis in the bone marrow of MM patients was confirmed in the present study. It seems that thalidomide is effective in the treatment of MM through the impairment of angiogenesis by decreasing FGF-2 and VEGF production. This is the first report on pathological evidence in the bone marrow of MM before and after thalidomide treatment, in Japan.
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PMID:Tumor angiogenesis in the bone marrow of multiple myeloma patients and its alteration by thalidomide treatment. 1508 32

Vascular endothelial growth factor and vascular endothelial growth factor receptors participate in the growth and survival of myeloid leukemic progenitors. With the development of multiple anti-angiogenic agents, there is potential that some of these novel agents will have anti-leukemic activity. Since these agents work by mechanisms distinct from current cytotoxic chemotherapies, they may be useful both in chemoresistant leukemia patients and in combinations to improve remission rates and remission durations.
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PMID:VEGF and myeloid leukemias. 1515 98

The antineoplastic compound aplidine, a new marine-derived depsipeptide, has shown preclinical activity in vitro on haematological and solid tumour cell lines. It is currently in early phase clinical trials. The exact mechanism of action of this anticancer agent still needs to be clarified. We have previously reported that aplidine blocks the secretion of the angiogenic factor vascular endothelial growth factor (VEGF) by the human leukaemia cells MOLT-4, suggesting a possible effect on tumour angiogenesis. This study was designed to investigate the antiangiogenic effect of aplidine. In vivo, in the chick embryo allantoic membrane (CAM) assay, aplidine inhibited spontaneous angiogenesis, angiogenesis elicited by exogenous VEGF and FGF-2, and induced by VEGF overexpressing 1A9 ovarian carcinoma cells. In vitro, at concentrations achievable in the plasma of patients, aplidine inhibited endothelial cell functions related to angiogenesis. It affected VEGF- and FGF-2-induced endothelial cell proliferation, inhibited cell migration and invasiveness assessed in the Boyden chamber and blocked the production of matrix metalloproteinases (MMP-2 and MMP-9) by endothelial cells. Finally, aplidine prevented the formation of capillary-like structures by endothelial cells on Matrigel. These findings indicate that aplidine has antiangiogenic activity in vivo and inhibits endothelial cell functional responses to angiogenic stimuli in vitro. This effect might contribute to the antineoplastic activity of aplidine.
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PMID:Antiangiogenic activity of aplidine, a new agent of marine origin. 1517 57

The oncoprotein Tax of human T-cell leukemia virus type I (HTLV-1) is the major mediator of viral pathogenesis in infected individuals. Expression of Tax under the regulation of the human granzyme B promoter in mice results in a lymphoproliferative disorder resembling adult T-cell leukemia/lymphoma (ATL). Tax expression is associated with the production of high levels interferon-gamma (IFN-gamma) in HTLV-1-infected CD4(+) cells and Tax-transgenic tumors. We examined the role of IFN-gamma in tumorigenesis, by mating Tax-transgenic mice with a gene-specific knockout for IFN-gamma. IFN-gamma(-/-) Tax(+)-transgenic mice show accelerated tumor onset (median, 4 versus 6 months), dissemination (median, 5 versus 7 months), and death (median, 7 versus 10 months), compared with IFN-gamma(+/-) or IFN-gamma(+/+) Tax(+) mice. Pathologic and immunophenotypic characteristics of tumors from all genotypes are indistinguishable, except for enhanced interleukin 2 receptor-beta (IL-2Rbeta) and suppressed intercellular adhesion molecule-1 (ICAM-1) expression on tumors from IFN-gamma(-/-) Tax(+) transgenic mice. IFN-gamma(-/-) tumors demonstrate enhanced CD31 (platelet-endothelial CAM-1 [PECAM-1]) staining compared with those from IFN-gamma(+/-) or IFN-gamma(+/+) Tax(+) mice. Angiogenesis-specific cDNA microarray analysis identified 4 mediators of angiogenic growth differentially expressed in tumors from Tax(+)IFN-gamma(-/-) mice compared with Tax(+)IFN-gamma(+/+) littermates. As confirmed by reverse transcription-polymerase chain reaction (RT-PCR), loss of IFN-gamma results in down-regulation of tumor necrosis factor-alpha (TNF-alpha) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) while up-regulating expression of vascular endothelial growth factor (VEGF) and tenascin C. These results provide insight into a possible mechanism by which IFN-gamma contributes to host resistance against HTLV-induced tumors through an angiostatic effect.
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PMID:Enhanced tumorigenesis in HTLV-1 tax-transgenic mice deficient in interferon-gamma. 1529 59

Hematopoietic cells and endothelial cells are mutually correlated in their development and growth. Various angiogenic factors, such as vascular endothelial growth factor (VEGF) and angiopoietins (Angs), are thought to be associated with leukemia cell growth. In this study, we examined if the Angs-Tie2 autocrine pathway works in primary AML cells or not by using soluble Tie2-Fc, which inhibits Angs from binding to Tie2 receptor. After 48 h of culture with Tie2-Fc, nine AML cells from 19 examined samples were not influenced by Tie2-Fc (group A), while AML cells from remaining 10 patients demonstrated remarkable reduction of cell number by Tie2-Fc treatment (group B). Tie2 receptor, upon binding to Angs, are known to activate phosphatidyl-inositol 3 kinase (PI3 kinase). Then, we examined the effect of LY294002, a potent PI3 kinase inhibitor, on primary AML cells. Cell number reduction effect by the treatment of LY294002 was much more prominent in cells of group B than of group A. In addition, extent of cell number reduction by Tie2-Fc and LY294002 was quite well correlated. These observations demonstrated that cells from a part of AML were dependent on autocrine Angs-Tie2 pathway. This notion was further supported by the study of two AML cell lines, KG-1 and HL-60: the growth of KG-1 was suppressed by Tie2-Fc, and also by anti-Tie2 antibody, which inhibits receptor-ligand interaction, while that of HL-60 was not suppressed by Tie2-Fc or anti-Tie2 antibody. Our results will help to explore the angiogenesis-oriented or endothelial cell-mediated therapy for leukemia.
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PMID:Autocrine pathway of angiopoietins-Tie2 system in AML cells: association with phosphatidyl-inositol 3 kinase. 1529 53

Human blood dendritic cells (DC) comprise plasmacytoid DC (PDC) and myeloid DC (MDC), which both prime antitumor T-cell responses. We prospectively monitored blood DC in 30 chronic myeloid leukemia (CML) patients before and after imatinib mesylate therapy. We found a dramatic reduction in PDC and MDC prior treatment. This reduction was associated with high plasmatic vascular endothelial growth factor (VEGF), a central regulator of angiogenesis which also participates to tumor-associated immune deficiencies. Phenotypic analysis of DC revealed in some patients a deficient expression of BDCA-4/neuropilin-1 on PDC, a molecule involved in angiogenesis and DC-T-cell interactions. High VEGF correlated to an altered Th1/Th2 balance in vivo and shifted PDC-induced T-cell polarization towards Th2 in vitro. Upon imatinib treatment, plasmatic VEGF rapidly decreased and a normal BDCA-4 expression was restored. PDC and MDC increased but did not reach the levels observed in healthy individuals. We conclude that VEGF may be a key player in blood DC deficiency in CML and we show that imatinib inhibits VEGF overproduction. Incomplete recovery of blood DC under imatinib despite VEGF normalization suggests a negative impact of this drug on dendritopoiesis in vivo and may result in a sustained defect in DC-mediated anti-CML responses.
Leukemia 2004 Oct
PMID:Defective blood dendritic cells in chronic myeloid leukemia correlate with high plasmatic VEGF and are not normalized by imatinib mesylate. 1534 47

Kaposi's sarcoma-associated herpesvirus (KSHV) is etiologically associated with several cancers including Kaposi's sarcoma (KS), primary effusion lymphoma, and multicentric Castleman's disease. KSHV-mediated pathogenesis is dependent mainly on KSHV infection as well as on the microenvironment provided by the growth factors (GFs)/inflammatory cytokines (ICs). Recently, we determined that oncoprotein Raf enhances KSHV infection of target cells. Interestingly, Raf regulates the expression of a variety of GFs/ICs including those involved in angiogenesis such as vascular endothelial growth factor (VEGF). In this review, we discuss the effect of the Raf-GF/IC autocrine/paracrine loop on KSHV infection of both hematopoietic and nonhematopietic cells, and associated disease conditions.
Leukemia 2005 Jan
PMID:Raf and VEGF: emerging therapeutic targets in Kaposi's sarcoma-associated herpesvirus infection and angiogenesis in hematopoietic and nonhematopoietic tumors. 1547 Apr 86

Besides its role as an essential regulator of physiologic and pathologic angiogenesis, vascular endothelial growth factor (VEGF) triggers growth, survival, and migration of leukemia and multiple myeloma cells; plays a pivotal role in hematopoiesis; inhibits maturation of dendritic cells; and increases osteoclastic bone-resorbing activity as well as osteoclast chemotaxis. Dysregulation of VEGF expression and signaling pathways therefore plays an important role in the pathogenesis and clinical features of hematologic malignancies, in particular multiple myeloma. Direct and indirect targeting of VEGF and its receptors therefore may provide a potent novel therapeutic approach to overcome resistance to therapies and thereby improve patient outcome.
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PMID:The pathophysiologic role of VEGF in hematologic malignancies: therapeutic implications. 1547 51

Fluorescent-labeled DNA probes were used to study 52 chronic lymphocytic leukemia (B-CLL) patients for (1) disease progression, (2) angiogenesis genes, (3) T-cell leukemia 1 gene (TCL1), (4) immunoglobulin heavy chain variable region (IGHv) and (5) chromosome 6q. Compared to stable disease, more patients with progressive disease had > or =2 anomalies and a high percentage of neoplastic nuclei. Anomalies of genes for basic fibroblast growth factor, interleukin 4, vascular endothelial growth factor or TCL1 were not detected. Deletions in IGHv occurred in 25% of patients and correlated with IGHv gene expression. Probes for 6q23 detected more deletions in 6q than probes for 6q21.
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PMID:Fluorescent-labeled DNA probes applied to novel biological aspects of B-cell chronic lymphocytic leukemia. 1566 Dec 60


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