9 results on '"Nör, J. E."'
Search Results
2. Antiangiogenic gene therapy: disruption of neovascular networks mediated by inducible caspase-9 delivered with a transcriptionally targeted adenoviral vector
- Author
-
Song, W, Sun, Q, Dong, Z, Spencer, D M, Núñez, G, and Nör, J E
- Published
- 2005
- Full Text
- View/download PDF
3. SHED Differentiate into Functional Odontoblasts and Endothelium.
- Author
-
Sakai, V. T., Zhang, Z., Dong, Z., Neiva, K. G., Machado, M. A. A. M., Shi, S., Santos, C. F., and Nör, J. E.
- Subjects
STEM cells ,DECIDUOUS teeth ,ENDOTHELIUM ,TISSUE engineering ,NEOVASCULARIZATION ,TRANSGENIC mice ,DENTAL pulp ,TETRACYCLINE ,GENE silencing ,POLYMERASE chain reaction ,WESTERN immunoblotting - Abstract
Studies on mechanisms underlying the differentiation of dental pulp stem cells are critical for the understanding of the biology of odontogenesis and for dental tissue engineering. Here, we tested the hypothesis that stem cells from exfoliated deciduous teeth (SHED) differentiate into functional odontoblasts and endothelial cells. SHED were seeded in tooth slice/scaffolds and implanted subcutaneously into immunodeficient mice. SHED differentiated into functional odontoblasts that generated tubular dentin, as determined by tetracycline staining and confocal microscopy. These cells also differentiated into vascular endothelial cells, as determined by beta-galactosidase staining of LacZ-tagged SHED. In vitro, vascular endothelial growth factor (VEGF) induced SHED to express VEGFR2, CD31, and VE-Cadherin (markers of endothelium) and to organize into capillary-like sprouts. VEGF induced ERK and AKT phosphorylation (indicative of differentiation), while inhibiting phosphorylation of STAT3 (indicative of 'stemness'). Collectively, this work demonstrates that SHED can differentiate into angiogenic endothelial cells and odontoblasts capable of generating tubular dentin. [ABSTRACT FROM AUTHOR]
- Published
- 2010
- Full Text
- View/download PDF
4. VEGF-dependent tumor angiogenesis requires inverse and reciprocal regulation of VEGFR1 and VEGFR2.
- Author
-
Zhang, Z., Neiva, K. G., Lingen, M. W., Ellis, L. M., and Nör, J. E.
- Subjects
VASCULAR endothelial growth factors ,NEOVASCULARIZATION ,CANCER patients ,REGULATION of cell growth ,EPITHELIUM - Abstract
Vascular endothelial growth factor (VEGF) signaling is critical for tumor angiogenesis. However, therapies based on inhibition of VEGF receptors (VEGFRs) have shown modest results for patients with cancer. Surprisingly little is known about mechanisms underlying the regulation of VEGFR1 and VEGFR2 expression, the main targets of these drugs. Here, analysis of tissue microarrays revealed an inversely reciprocal pattern of VEGFR regulation in the endothelium of human squamous-cell carcinomas (high VEGFR1, low VEGFR2), as compared with the endothelium of control tissues (low VEGFR1, high VEGFR2). Mechanistic studies demonstrated that VEGF signals through the Akt/ERK pathway to inhibit constitutive ubiquitination and induce rapid VEGFR1 accumulation in endothelial cells. Surprisingly, VEGFR1 is primarily localized in the nucleus of endothelial cells. In contrast, VEGF signals through the JNK/c-Jun pathway to induce endocytosis, nuclear translocation, and downregulation of VEGFR2 via ubiquitination. VEGFR1 signaling is required for endothelial-cell survival, while VEGFR2 regulates capillary tube formation. Notably, the antiangiogenic effect of bevacizumab (anti-VEGF antibody) requires normalization of VEGFR1 and VEGFR2 levels in human squamous-cell carcinomas vascularized with human blood vessels in immunodeficient mice. Collectively, this work demonstrates that VEGF-induced angiogenesis requires inverse regulation of VEGFR1 and VEGFR2 in tumor-associated endothelial cells. [ABSTRACT FROM AUTHOR]
- Published
- 2010
- Full Text
- View/download PDF
5. Angiogenic Signaling Triggered by Cariogenic Bacteria in Pulp Cells.
- Author
-
Soden, R. I., Botero, T. M., Hanks, C. T., and Nör, J. E.
- Subjects
NEOVASCULARIZATION ,BACTERIA ,DENTAL pulp ,ENDOTOXINS ,ENDODONTICS ,INFLAMMATION ,VASCULAR endothelial growth factors ,PULPITIS ,STREPTOCOCCUS - Abstract
The inflammation observed in the dental pulp of teeth with deep caries lesions is characterized by a significant increase in blood vessel density. It is known that lipoteichoic acid (LTA) from Grampositive cariogenic bacteria induces expression of vascular endothelial growth factor (VEGF) in dental pulp cells. The hypothesis underlying this study was that LTA induces VEGF expression in dental pulp cells through TLR2 and PI3k/Akt signaling. Odontoblast-like cells (MDPC-23) and undifferentiated pulp cells (OD-21) were exposed to LTA from Streptococcus sanguis, and the role of TLR2, PI3K/Akt, and IKK signaling in LTA-induced VEGF expression was evaluated. These studies demonstrated that TLR2 signaling through the PI3K-Akt pathway is necessary for LTA-induced VEGF expression in pulp cells. In contrast, inhibition of IKK signaling did not prevent VEGF up-regulation in response to LTA. Understanding signaling pathways triggered by cariogenic bacteria may reveal novel therapeutic targets for the clinical management of pulpitis. [ABSTRACT FROM AUTHOR]
- Published
- 2009
- Full Text
- View/download PDF
6. Effect of PTK/ZK on the Angiogenic Switch in Head and Neck Tumors.
- Author
-
Miyazawa, M., Dong, Z., Zhang, Z., Neiva, K. G., Cordeiro, M. M., Oliveira, D. T., and Nör, J. E.
- Subjects
NEOVASCULARIZATION ,VASCULAR endothelial growth factors ,HEAD tumors ,NECK tumors ,CANCER treatment ,MICRODISSECTION - Abstract
Transformation of small avascular masses of tumor cells into rapidly progressive cancers is triggered by the angiogenic switch, a process that involves vascular endothelial growth factor (VEGF) signaling. We have shown that VEGF enhances the survival and angiogenic potential of endothelial cells by activating the Bcl-2-CXCL8 signaling axis. The purpose of this study was to evaluate the effect of a small-molecule inhibitor of VEGF receptors (PTK/ZK) on the initial stages of head and neck tumor angiogenesis. In vitro, PTK/ ZK blocked head and neck tumor cell (OSCC3 or UM-SCC-17B)-induced Bcl-2 and CXCL8 expression in endothelial cells. Oral administration of PTK/ZK decreased xenograft head and neck tumor microvessel density, and inhibited Bcl-2 and CXCL8 expression in tumor-associated endothelial cells. Analysis of these data demonstrates that PTK/ZK blocks downstream targets of VEGF signaling in endothelial cells, and suggests that PTK/ZK may inhibit the angiogenic switch in head and neck tumors. Abbreviations: HDMEC, human dermal microvascular endothelial cells; VEGF, vascular endothelial growth factor; CXCL8, CXC ligand-8; PTK/ZK, PTK787/ZK222584. [ABSTRACT FROM AUTHOR]
- Published
- 2008
- Full Text
- View/download PDF
7. Effects of VEGF and FGF2 on the Revascularization of Severed Human Dental Pulps.
- Author
-
Mullane, E. M., Dong, Z., Sedgley, C. M., Hu, J. C.-C., Botero, T. M., Holland, G. R., and Nör, J. E.
- Subjects
DENTAL pulp ,BLOOD vessels ,NEOVASCULARIZATION ,FIBROBLAST growth factors ,VASCULAR endothelial growth factors ,MOLARS - Abstract
The long-term outcome of replanted avulsed permanent teeth is frequently compromised by lack of revascularization, resulting in pulp necrosis. The purpose of this study was to evaluate the effects of vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF-2) on the revascularization of severed human dental pulps. Tooth slices were prepared from non-carious human molars and treated with 0-50 ng/mL rhVEGF
165 or rhFGF-2 for 7 days in vitro. Both angiogenic factors enhanced pulp microvessel density compared with untreated controls (p < 0.05). Tooth slices were also treated with 0 or 50 ng/mL rhVEGF165 for one hour prior to implantation into the subcutaneous space of immunodeficient mice. Treatment with rhVEGF165 increased pulp microvessel density in vivo (p < 0.05). These results demonstrate that rhVEGF165 enhanced neovascularization of severed human dental pulps and suggest that topical application of an angiogenic factor prior to replantation might be beneficial for the treatment of avulsed teeth. [ABSTRACT FROM AUTHOR]- Published
- 2008
- Full Text
- View/download PDF
8. Unidirectional crosstalk between Bcl-xL and Bcl-2 enhances the angiogenic phenotype of endothelial cells.
- Author
-
Karl, E., Zhang, Z., Dong, Z., Neiva, K. G., Soengas, M. S., Koch, A. E., Polverini, P. J., Núñez, G., and Nör, J. E.
- Subjects
VASCULAR endothelial growth factors ,ENDOTHELIAL seeding ,EPIDERMAL growth factor ,CHEMOKINES ,GENE expression ,APOPTOSIS - Abstract
Expression of Bcl-x
L correlates with the clinical outcomes of patients with cancer. While the role of Bcl-2 in angiogenesis is becoming increasingly evident, the function of Bcl-xL in angiogenesis is unclear. Here, we showed that epidermal growth factor (EGF) induces in vitro capillary sprouting and Bcl-xL expression in primary endothelial cells. Bcl-xL -transduced human dermal microvascular endothelial cells (HDMEC-Bcl-xL ), but not empty vector control cells, spontaneously organize into capillary-like sprouts. Searching for a mechanism to explain these responses, we observed that Bcl-xL induced expression of the pro-angiogenic chemokines CXC ligand-1 (CXCL1) and CXC ligand-8 (CXCL8), and that blockade of CXC receptor-2 (CXCR2) signaling inhibited spontaneous sprouting of HDMEC-Bcl-xL . Bcl-xL led to Bcl-2 upregulation, but Bcl-2 did not upregulate Bcl-xL , suggesting the existence of a unidirectional crosstalk from Bcl-xL to Bcl-2. EGF and Bcl-xL activate the mitogen-activated protein kinase/ERK pathway resulting in upregulation of vascular endothelial growth factor (VEGF), a known inducer of Bcl-2 in endothelial cells. Inhibition of VEGF receptor signaling in HDMEC-Bcl-xL prevented Bcl-2 upregulation and demonstrated the function of a VEGF-mediated autocrine loop. Bcl-2 downregulation by RNAi blocked CXCL1 and CXCL8 expression downstream of Bcl-xL , and markedly decreased angiogenesis in vivo. We conclude that Bcl-xL functions as a pro-angiogenic signaling molecule controlling Bcl-2 and VEGF expression. These results emphasize a complex interplay between Bcl-2 family members beyond their classical roles in apoptosis.Cell Death and Differentiation (2007) 14, 1657–1666; doi:10.1038/sj.cdd.4402174; published online 15 June 2007 [ABSTRACT FROM AUTHOR]- Published
- 2007
- Full Text
- View/download PDF
9. Activation of iCaspase-9 in Neovessels Inhibits Oral Tumor Progression.
- Author
-
Pinsky, M. S., Song, W., Dong, Z., Warner, K., Zeitlin, B., Karl, E., Hall, D. E., and Nör, J. E.
- Subjects
NEOVASCULARIZATION ,APOPTOSIS ,CELL death ,CELLS ,CYSTS (Pathology) ,CELLULAR pathology ,ORAL cancer ,TUMOR growth - Abstract
Tumors of the oral cavity are highly vascularized malignancies. Disruption of neovascular networks was shown to limit the access of nutrients and oxygen to tumor cells and inhibit tumor progression. Here, we evaluated the effect of the activation of an artificial death switch (iCaspase-9) expressed in neovascular endothelial cells on the progression of oral tumors. We used biodegradable scaffolds to co-implant human dermal microvascular endothelial cells stably expressing iCaspase-9 (HDMEC-iCasp9) with oral cancer cells expressing luciferase (OSCC3-luc or UM-SCC-17B-luc) in immunodeficient mice. Alternatively, untransduced HDMEC were co-implanted with oral cancer cells, and a transcriptionaly targeted adenovirus (Ad-VEGFR2-iCasp-9) was injected locally to deliver iCaspase-9 to neovascular endothelial cells. In vivo bioluminescence demonstrated that tumor progression was inhibited, and immunohisto-chemistry showed that microvessel density was decreased, when iCaspase-9 was activated in tumor-associated microvessels. We conclude that activation of iCaspase-9 in neovascular endothelial cells is sufficient to inhibit the progression of xenografted oral tumors. [ABSTRACT FROM AUTHOR]
- Published
- 2006
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.