The Experts below are selected from a list of 63 Experts worldwide ranked by ideXlab platform
Robert Clarke - One of the best experts on this subject based on the ideXlab platform.
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regulation of breast cancer stem cell activity by signaling through the Notch4 Receptor
Cancer Research, 2010Co-Authors: Hannah Harrison, Gillian Farnie, Sacha J Howell, Rebecca Rock, Spyros Stylianou, Keith Brennan, N J Bundred, Robert ClarkeAbstract:Notch signaling supports breast cancer stem cells that mediate disease recurrence after initial treatment, but Notch-targeted therapeutics that can selectively target signaling by the Notch4 Receptor may be the most effective.
Hannah Harrison - One of the best experts on this subject based on the ideXlab platform.
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regulation of breast cancer stem cell activity by signaling through the Notch4 Receptor
Cancer Research, 2010Co-Authors: Hannah Harrison, Gillian Farnie, Sacha J Howell, Rebecca Rock, Spyros Stylianou, Keith Brennan, N J Bundred, Robert ClarkeAbstract:Notch signaling supports breast cancer stem cells that mediate disease recurrence after initial treatment, but Notch-targeted therapeutics that can selectively target signaling by the Notch4 Receptor may be the most effective.
Patrick A Murphy - One of the best experts on this subject based on the ideXlab platform.
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constitutively active Notch4 Receptor elicits brain arteriovenous malformations through enlargement of capillary like vessels
Proceedings of the National Academy of Sciences of the United States of America, 2014Co-Authors: Patrick A Murphy, Lawrence Huang, Corinne M Nielsen, Michael T Lawton, Ralf H Adams, Chris B Schaffer, Rong WangAbstract:Abstract Arteriovenous (AV) malformation (AVM) is a devastating condition characterized by focal lesions of enlarged, tangled vessels that shunt blood from arteries directly to veins. AVMs can form anywhere in the body and can cause debilitating ischemia and life-threatening hemorrhagic stroke. The mechanisms that underlie AVM formation remain poorly understood. Here, we examined the cellular and hemodynamic changes at the earliest stages of brain AVM formation by time-lapse two-photon imaging through cranial windows of mice expressing constitutively active Notch4 (Notch4*). AVMs arose from enlargement of preexisting microvessels with capillary diameter and blood flow and no smooth muscle cell coverage. AV shunting began promptly after Notch4* expression in endothelial cells (ECs), accompanied by increased individual EC areas, rather than increased EC number or proliferation. Alterations in Notch signaling in ECs of all vessels, but not arteries alone, affected AVM formation, suggesting that Notch functions in the microvasculature and/or veins to induce AVM. Increased Notch signaling interfered with the normal biological control of hemodynamics, permitting a positive feedback loop of increasing blood flow and vessel diameter and driving focal AVM growth from AV connections with higher blood velocity at the expense of adjacent AV connections with lower velocity. Endothelial expression of constitutively active Notch1 also led to brain AVMs in mice. Our data shed light on cellular and hemodynamic mechanisms underlying AVM pathogenesis elicited by increased Notch signaling in the endothelium.
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Endothelial Notch signaling is upregulated in human brain arteriovenous malformations and a mouse model of the disease
Laboratory Investigation, 2009Co-Authors: Patrick A Murphy, Gloria Lu, Steven Shiah, Andrew W Bollen, Rong A WangAbstract:Brain arteriovenous malformations (BAVMs) can cause lethal hemorrhagic stroke and have no effective treatment. The cellular and molecular basis for this disease is largely unknown. We have previously shown that expression of constitutively-active Notch4 Receptor in the endothelium elicits and maintains the hallmarks of BAVM in mice, thus establishing a mouse model of the disease. Our work suggested that Notch pathway could be a critical molecular mediator of BAVM pathogenesis. Here, we investigated the hypothesis that upregulated Notch activation contributes to the pathogenesis of human BAVM. We examined the expression of the canonical Notch downstream target Hes1 in the endothelium of human BAVMs by immunofluorescence, and showed increased levels relative to either autopsy or surgical biopsy controls. We then analyzed Receptor activity using an antibody to the activated form of the Notch1 Receptor, and found increased levels of activity. These findings suggest that Notch activation may promote the development and even maintenance of BAVM. We also detected increases in Hes1 and activated Notch1 expression in our mouse model of BAVM induced by constitutively active Notch4, demonstrating molecular similarity between the mouse model and the human disease. Our work suggests that activation of Notch signaling is an important molecular candidate in BAVM pathogenesis and further validates that our animal model provides a platform to study the progression as well as the regression of the disease.
Gillian Farnie - One of the best experts on this subject based on the ideXlab platform.
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regulation of breast cancer stem cell activity by signaling through the Notch4 Receptor
Cancer Research, 2010Co-Authors: Hannah Harrison, Gillian Farnie, Sacha J Howell, Rebecca Rock, Spyros Stylianou, Keith Brennan, N J Bundred, Robert ClarkeAbstract:Notch signaling supports breast cancer stem cells that mediate disease recurrence after initial treatment, but Notch-targeted therapeutics that can selectively target signaling by the Notch4 Receptor may be the most effective.
Spyros Stylianou - One of the best experts on this subject based on the ideXlab platform.
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regulation of breast cancer stem cell activity by signaling through the Notch4 Receptor
Cancer Research, 2010Co-Authors: Hannah Harrison, Gillian Farnie, Sacha J Howell, Rebecca Rock, Spyros Stylianou, Keith Brennan, N J Bundred, Robert ClarkeAbstract:Notch signaling supports breast cancer stem cells that mediate disease recurrence after initial treatment, but Notch-targeted therapeutics that can selectively target signaling by the Notch4 Receptor may be the most effective.
