Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1519670 (tumor angiogenesis)
 6,052 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this study, we investigated the effects of human type I consensus interferon (IFN-con1) (Amgen) gene transfer into body cavity-based lymphomas (BCBL)-1 cells, which are latently infected with Kaposi's sarcoma-associated herpesvirus (KSHV) human herpesvirus-8 (HHV-8). Both the basal and 12-O-tetradecanoyl phorbol-13-acetate (TPA)-stimulated production of KSHV/HHV-8 mature virions was strongly inhibited in genetically modified IFN-producing BCBL-1 cells as compared with parental or control transduced counterparts. A similar inhibition was obtained on treatment of parental BCBL-1 cells with exogenous IFN-con1. The reduction in KSHV/HHV-8 production was associated with a decrease in the basal and TPA-stimulated intracellular amount of the linear form of the viral genome. Interestingly, 25%40% of the IFN-producing BCBL-1 cell population underwent spontaneous apoptosis in vitro. TPA treatment, which did not significantly affect the viability of the parental and control BCBL-1 cells, resulted in the apoptotic death of up to 70% of the IFN-producing cell population. Addition of exogenous IFN-con1 to parental BCBL-1 cells produced similar effects, although less intense. Injection of either parental or control-transduced BCBL-1 cells into SCID mice resulted in progressively growing tumors characterized by an unusually high level of tumor angiogenesis. In contrast, complete tumor regression was observed in all the mice injected either subcutaneously (s.c.) or intraperitoneally (i.p.) with the IFN-producing BCBL-1 cells. These results represent the first evidence that type I IFN can counteract the activation of a productive herpesvirus infection in latently infected tumor cells by the induction of apoptosis, providing an interesting link between the antiviral and antitumor activities of this cytokine. These data suggest the possible advantages of strategies of type I IFN gene transfer (with respect to the use of the exogenous cytokine) for the treatment of patients with some HHV-8-induced malignancies.
J Interferon Cytokine Res 1999 Nov
PMID:Type I consensus IFN (IFN-con1) gene transfer into KSHV/HHV-8-infected BCBL-1 cells causes inhibition of viral lytic cycle activation via induction of apoptosis and abrogates tumorigenicity in sCID mice. 1057 24

Recent studies have shown that interleukin-8 (IL-8) plays an important role in the growth and metastasis of human pancreatic cancer. In the present study, we determined the molecular regulation of constitutive IL-8 expression in human pancreatic cancer cells. Various human pancreatic cancer cell lines were incubated in vitro. Sixty-seven percent of the cell lines constitutively secreted high levels of IL-8, as determined using enzyme-linked immunosorbent assay. Consistently, these cells constitutively expressed high levels of IL-8 mRNA, as determined using Northern blot analysis. To determine the mechanisms of the high steady-state levels of IL-8 mRNA, the IL-8 half-life and transcription rate were measured. There was no significant difference in IL-8 half-life between cells expressing high and low levels of IL-8. However, higher transcription rates and increased IL-8 promoter activity were observed in the cells constitutively expressing high levels of IL-8. Detailed IL-8 promoter analysis using deletion mutation revealed that the region from -85 to -133 bp was essential for the constitutive IL-8 promoter activity. Also, point-mutation analysis indicated that mutation of NF-kappaB, AP-1, or NF-IL-6 binding sites significantly reduced or eliminated the constitutive IL-8 promoter activity. Consistent with the constitutive IL-8 transcription activity, high levels of constitutive NF-kappaB and AP-1 activity were detected in the cells overexpressing IL-8, as determined using electrophoretic mobility shift assay. In addition, transfection of a dominant-negative I-kappaBalpha expression vector (I-kappaBalphaM) inhibited constitutive NF-kappaB activity and IL-8 expression in pancreatic cancer cells. Collectively, our data demonstrated that constitutive NF-kappaB and AP-1 activation contributes to the overexpression of IL-8, which in turn plays an important role in tumor angiogenesis and contributes to the aggressive biology of human pancreatic cancer.
J Interferon Cytokine Res 2000 Nov
PMID:Molecular regulation of constitutive expression of interleukin-8 in human pancreatic adenocarcinoma. 1109 50

In murine macrophages, the anti-tumor agent, paclitaxel, induces expression of a wide variety of inflammatory and anti-inflammatory genes, and causes cytokine secretion via signaling pathways that overlap with those engaged by lipopolysaccharide (LPS), the endotoxic component of Gram-negative bacteria. Using semi-quantitative RT-PCR for detection of gene expression, coupled with ELISA for the detection of secreted gene products, we analyzed the responsiveness of an extensive panel of cytokine and non-cytokine genes to induction by paclitaxel and LPS in the murine DA-3 breast cancer line. A subset of the genes examined (e.g., G-CSF, MIP-2, iNOS, and IL-1 beta, and GM-CSF) was upregulated >3-20-fold by both LPS and paclitaxel in the DA-3 cell line, while IP-10 mRNA was induced by paclitaxel, but not by LPS. In the human MDA-MB-231 breast cancer cell line, LPS also increased mRNA levels for both GM-CSF and IP-10 significantly, while, paclitaxel increased IP-10 mRNA levels with delayed kinetics and failed to induce GM-CSF mRNA. Co-cultures of murine breast cancer cells and macrophages, stimulated with IFN-gamma plus either paclitaxel or LPS, resulted in augmented release of nitric oxide. As both GM-CSF and IP-10 have been implicated in tumor rejection in vivo through either indirect actions on the host immune system or by inhibiting tumor angiogenesis, our data strengthen the hypothesis that tumor cell-derived inflammatory mediators may, in part, underlie the anti-tumor efficacy of paclitaxel in breast cancer.
Cytokine 2001 Aug 07
PMID:Induction of proinflammatory and chemokine genes by lipopolysaccharide and paclitaxel (Taxol) in murine and human breast cancer cell lines. 1155 85

Eph receptors are a unique family of receptor tyrosine kinases that play critical roles in embryonic patterning, neuronal targeting, vascular development and adult neovascularization. Engagement of Eph receptors by ephrin ligands mediates critical steps of angiogenesis, including juxtacrine cell-cell contacts, cell adhesion to extracellular matrix, and cell migration. Recent evidence from in vitro angiogenesis assays and analysis of mice deficient for one or more members of the Eph family establishes the role of Eph signaling in sprouting angiogenesis and blood vessel remodeling during vascular development. Furthermore, elevated expression of Eph receptors and ephrin ligands is associated with tumors and associated tumor vasculature, suggesting that Eph receptors and their ephrin ligands also play critical roles in tumor angiogenesis and tumor growth. This review will focus on the relevance of Eph receptor signaling in embryonic and adult neovascularization, and possible contributions to tumor growth and metastasis.
Cytokine Growth Factor Rev 2002 Feb
PMID:The ephrins and Eph receptors in angiogenesis. 1175 Aug 81

PDGFs and their cognate tyrosine kinase alpha- and beta-receptors are involved in multiple tumor-associated processes including autocrine growth stimulation of tumor cells, stimulation of tumor angiogenesis and recruitment and regulation of tumor fibroblasts. The recent development of clinically useful PDGF antagonists, like STI571/Glivec, has increased the interest in PDGF receptors as cancer drug targets. Autocrine PDGF receptor signaling occurs in certain malignancies characterized by mutational activation of PDGF or PDGF receptors, for instance, dermatofibrosaracoma protuberans, gastrointestinal stromal tumors, and hypereosinophilic syndrome. The roles of PDGF in regulation of tumor angiogenesis and tumor fibroblasts are more general, and probably occur in most common solid tumors. Concerning tumor angiogenesis recent studies have predominantly focused on the importance of PDGF receptor signaling for tumor pericyte recruitment. PDGF receptors in the tumor stroma have also attracted attention as interesting drug targets because of their function as regulators of tumor interstitial fluid pressure, tumor transvascular transport and tumor drug uptake. In summary, the improved understanding of the role of PDGF signaling in tumor biology, and the introduction of PDGF antagonists, has set the stage for a continued development of PDGF antagonists as novel cancer drugs.
Cytokine Growth Factor Rev 2004 Aug
PMID:PDGF receptors-mediators of autocrine tumor growth and regulators of tumor vasculature and stroma. 1520 17

Vascular endothelial growth factor (VEGF), which was originally discovered as vascular permeability factor, is critical to human cancer angiogenesis through its potent functions as a stimulator of endothelial cell survival, mitogenesis, migration, differentiation and self-assembly, as well as vascular permeability, immunosuppression and mobilization of endothelial progenitor cells from the bone marrow into the peripheral circulation. Genetic alterations and a chaotic tumor microenvironment, such as hypoxia, acidosis, free radicals, and cytokines, are clearly attributed to numerous abnormalities in the expression and signaling of VEGF and its receptors. These perturbations confer a tremendous survival and growth advantage to vascular endothelial cells as manifested by exuberant tumor angiogenesis and a consequent malignant phenotype. Understanding the regulatory mechanisms of both inducible and constitutive VEGF expression will be crucial in designing effective therapeutic strategies targeting VEGF to control tumor growth and metastasis. In this review, molecular regulation of VEGF expression in tumor cells is discussed.
Cytokine Growth Factor Rev 2004 Oct
PMID:Constitutive and inducible expression and regulation of vascular endothelial growth factor. 1545 Feb 48

Vascular endothelial growth factor (VEGF) is critical for vascularization of tissues, including tumors, making it an attractive target for controlling angiogenesis. An important first step towards the goal of effectively blocking tumor angiogenesis is to understand the relationships among tumor-promoting molecules. Whereas little is known about developmental regulation of VEGF, pathological regulation of VEGF during disease states and tumorigenesis is better understood. This review focuses on transcriptional regulation of VEGF expression in cancer. Understanding how VEGF is regulated in tumors cells may provide the basis for future treatments that target both the tumor and its vascular supply.
Cytokine Growth Factor Rev 2005 Feb
PMID:Transcriptional regulation of vascular endothelial growth factor in cancer. 1573 33

Tumor angiogenesis is stimulated by a pro-angiogenic shift in both inducers and inhibitors of endothelial growth. To study this shift, we measured serum and plasma levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), endostatin, and thrombospondin 1 (TSP1) in 21 advanced non-small cell lung cancer (NSCLC) patients and 46 healthy control subjects. In addition, we assessed the relevance of these levels to disease outcome. Cytokine levels were prospectively measured in plasma and serum by enzyme-linked immunosorbent assay at three times: before chemotherapy and at 1 and 12 weeks following initiation of chemotherapy. In NSCLC patients, serum VEGF levels (sVEGF) were elevated (p<0.001), whereas serum and plasma TSP1 levels were lower (p=0.012 and p=0.004, respectively) than in healthy control subjects. Pretreatment plasma endostatin and serum bFGF levels were higher in NSCLC patients than in healthy controls (p=0.05 and 0.01, respectively). Change in sVEGF at week 12 after initiation of chemotherapy correlated with response to therapy (p=0.002). Patients with pretreatment sVEGF levels <500 pg/mL had a median survival of 11 months, but those with sVEGF >500 pg/mL had only a 6 months' median survival (p < 0.03). In NSCLC patients, VEGF levels are increased, whereas TSP1 levels are decreased, which may trigger and sustain tumor angiogenesis. High levels of serum VEGF at the time of presentation with NSCLC may predict worse survival.
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PMID:Circulating angiogenic cytokines in patients with advanced non-small cell lung cancer: correlation with treatment response and survival. 1594 4

Hypoxia-inducible factor-1 (HIF-1) is a dimeric transcriptional complex that has been recognized primarily for its role in the maintenance of oxygen and energy homoeostasis. The HIF-1alpha subunit is O(2) labile and is degraded by the proteasome following prolyl-hydroxylation and ubiquitination in normoxic cells. The present review summarizes evidence that HIF-1 is also involved in immune reactions. Immunomodulatory peptides, including interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha), stimulate HIF-1 dependent gene expression even in normoxic cells. Both the hypoxic and the cytokine-induced activation of HIF-1 involve the phosphatidylinositol- 3-kinase (PI3K) and the mitogen-activated protein kinase (MAPK) signaling pathways. In addition, heat shock proteins (HSP) and other cofactors interact with HIF-1 subunits. HIF-1 increases the transcription of several genes for proteins that promote blood flow and inflammation, including vascular endothelial growth factor (VEGF), heme oxygenase-1, endothelial and inducible nitric oxide synthase (NOS) and cyclooxygenase-2 (COX-2). The pharmacologic activation of the HIF-1 complex can be desirable in ischemic and inflammatory disorders. In contrast, HIF-1 blockade may be beneficial to prevent tumor angiogenesis and tumor growth.
J Interferon Cytokine Res 2005 Jun
PMID:Review: hypoxia-inducible factor-1 (HIF-1): a novel transcription factor in immune reactions. 1595 53

Nerves and blood vessels resemble each other in their ability to form branching networks. They are in close proximity suggesting possible molecular interactions. The patterning of nerves and blood vessels are not random but are regulated by attractive and repulsive cues. Four major neuronal guidance factors that are sensed by growth cones have been identified, Semaphorin, Ephrin, Slit and Netrin, and their cognate receptors, neuropilin, Eph, roundabouts (Robo) and uncoordinated-5 (UNC5). Unexpectedly, these ligand/receptor pairs also regulate developmental and tumor angiogenesis. Together, there is strong evidence that development of the nervous and vascular systems are regulated by common cues.
Cytokine Growth Factor Rev
PMID:A role for axon guidance receptors and ligands in blood vessel development and tumor angiogenesis. 1597 25


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