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Bishop, Eileen; Bell, Graham; Bloor, Stephen J.; Broom, Iain; Hendry, Neil F.K.; Wheatley, Denys N.

doi:10.1023/a:1026546219962

Cited by 280 publications

(121 citation statements)

References 15 publications

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“…As represented in the Figure S2B, tubule-formation activity measured after 24 hours of exposure to either SEN461 or the tankyrase inhibitor XAV939 [31] did not produce any change compared to DMSO treated HT-1080 cells. On the contrary, Suramin at a concentration of 3 µmol/L [40] induced a complete abrogation of tubule formation (data not shown). Moreover, SEN461 did not show any effect on tubule-formation activity, even on HUVEC cells (data not shown).…”

Section: Resultsmentioning

confidence: 83%

Human Sarcoma Growth Is Sensitive to Small-Molecule Mediated AXIN Stabilization

et al. 2014

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Sarcomas are mesenchymal tumors showing high molecular heterogeneity, reflected at the histological level by the existence of more than fifty different subtypes. Genetic and epigenetic evidences link aberrant activation of the Wnt signaling to growth and progression of human sarcomas. This phenomenon, mainly accomplished by autocrine loop activity, is sustained by gene amplification, over-expression of Wnt ligands and co-receptors or epigenetic silencing of endogenous Wnt antagonists. We previously showed that pharmacological inhibition of Wnt signaling mediated by Axin stabilization produced in vitro and in vivo antitumor activity in glioblastoma tumors. Here, we report that targeting different sarcoma cell lines with the Wnt inhibitor/Axin stabilizer SEN461 produces a less transformed phenotype, as supported by modulation of anchorage-independent growth in vitro. At the molecular level, SEN461 treatment enhanced the stability of the scaffold protein Axin1, a key negative regulator of the Wnt signaling with tumor suppressor function, resulting in downstream effects coherent with inhibition of canonical Wnt signaling. Genetic phenocopy of small molecule Axin stabilization, through Axin1 over-expression, coherently resulted in strong impairment of soft-agar growth. Importantly, sarcoma growth inhibition through pharmacological Axin stabilization was also observed in a xenograft model in vivo in female CD-1 nude mice. Our findings suggest the usefulness of Wnt inhibitors with Axin stabilization activity as a potentialyl clinical relevant strategy for certain types of sarcomas.

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Section: Resultsmentioning

confidence: 83%

Human Sarcoma Growth Is Sensitive to Small-Molecule Mediated AXIN Stabilization

et al. 2014

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“…Measurement of Angiogenic Activities-Angiogenic activities of the conditioned medium were measured with an angiogenesis kit (KURABO) according to the protocol by the manufacturer (23). Cardiac myocytes (5 ϫ 10 6 cells/well) were incubated with adenoviral vectorexpressing ␤-galactosidase or caSTAT3 at a moi 20 in M-199 with 2% fetal calf serum for 12 h. After transfection, cells were washed three times and cultured in 1 ml of serum-depleted M-199 for 24 h. An equal amount of the conditioned medium from the cardiac myocyte culture was added to the basal medium of the human umbilical vein endothelial cell (HUVEC)/fibroblast co-culture.…”

Section: Methodsmentioning

confidence: 99%

Cardiac-specific Activation of Signal Transducer and Activator of Transcription 3 Promotes Vascular Formation in the Heart

Osugi

Oshima

Fujio

et al. 2002

Journal of Biological Chemistry

141

101

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Signal transducer and activator of transcription 3 (STAT3) functions in cell proliferation, differentiation, and cell survival. Previously, we have demonstrated that the activation of STAT3 is required for glycoprotein 130-mediated induction of VEGF in cardiac myocytes, but the functional importance of STAT3 as an angiogenic mediator remains to be determined. To address this issue, we first generated the adenoviral vector expressing constitutively active STAT3 (caSTAT3). Adenoviral gene transfer of caSTAT3 induced an increase in the expression of VEGF in cultured cardiomyocytes. The conditioned medium from caSTAT3-transfected cardiomyocyte culture promoted endothelial tubule formation, which was inhibited by anti-VEGF antibody. Next, we generated the transgenic (TG) mice with cardiacspecific overexpression of caSTAT3 and demonstrated that caSTAT3 TG mice showed evidence of VEGF induction in the hearts. The caSTAT3 TG hearts also demonstrated increased capillary density accompanied by an increase in the expression of VE-cadherin, an endothelial-specific component. These data indicate that caSTAT3 TG hearts exhibit an enriched vascular structure compared with non-transgenic hearts. The study presented here provides the first evidence that activation of STAT3 controls vessel growth in vivo and suggests that STAT3 contributes to cardiac adaptation by regulating vascular function under the conditions of stress.

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“…We used an angiogenesis kit (Kurabo Co.) according to the manufacturer's protocol [21,22]. Briefly, HUVECs and fibroblasts were cocultured in 24-well plates with basal medium only (control) or basal medium containing VEGF or IL-8 (1 or 10 ng/ml).…”

Section: Huvec Tube-formation Assay For Angiogenesismentioning

confidence: 99%

Proteasome Inhibitor MG132 Inhibits Angiogenesis in Pancreatic Cancer by Blocking NF-κB Activity

et al. 2009

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Since angiogenesis enables solid tumors, including pancreatic cancer (PaCa), to grow and metastasize, the development of anti-angiogenic agents is currently one of the urgent issues. Proteasome inhibitors are well known for inhibiting nuclear factor-kappa B (NF-kappaB) activity in various cancer cells, but little is known about their biologic mechanisms against angiogenesis in PaCa. We divided human PaCa cell lines into high-angiogenic (BxPC-3 and SW 1990) and low-angiogenic (MIA PaCa-2 and Capan-2) groups. The high-angiogenic PaCa cell lines constitutively expressed high NF-kappaB activity and produced high levels of vascular endothelial growth factor (VEGF) and interleukin 8 (IL-8). The conditioned media from BxPC-3 significantly enhanced both proliferation of and tube formation by human umbilical vein endothelial cells (HUVECs) and these enhancements were significantly inhibited by the proteasome inhibitor MG132 treatment. Collectively, MG132 blocked PaCa-derived VEGF and IL-8 production through inhibition of NF-kappaB activity. Thus, proteasome inhibitors may prove beneficial as anti-angiogenic therapy for PaCa. Our studies show that MG132, a proteasome inhibitor, significantly blocked pancreatic-cancer-associated angiogenesis through inhibition of NF-kappaB and NF-kappaB-dependent proangiogenic gene products VEGF and IL-8.

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Untitled

Cited by 280 publications

References 15 publications

Human Sarcoma Growth Is Sensitive to Small-Molecule Mediated AXIN Stabilization

Human Sarcoma Growth Is Sensitive to Small-Molecule Mediated AXIN Stabilization

Cardiac-specific Activation of Signal Transducer and Activator of Transcription 3 Promotes Vascular Formation in the Heart

Proteasome Inhibitor MG132 Inhibits Angiogenesis in Pancreatic Cancer by Blocking NF-κB Activity

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