Search results for "Angiogenesis"
showing 10 items of 552 documents
Matrix metalloproteinases 2 and 9, and extracellular matrix in Kaposi's sarcoma
2010
Matrix metalloproteinases (MMPs) are associated with Kaposi's sarcoma (KS) tumorigenesis and may contribute to the mechanism of KS invasive growth. To date, only a few MMPs have been studied in KS lesions, and exactly which MMPs are involved in KS development and progression remains unanswered. However, MMPs 2 and 9 have been associated with different phases of angiogenesis, but their role in the proteolytic modification of the extracellular matrix has not been investigated. The results of this study confirm that MMPs, specifically MMP-2 and MMP-9, can contribute to angiogenesis by disrupting the vessel basement membrane and other extracellular matrix barriers, and enabling endothelial cell…
Molecular mechanisms of sorafenib action in liver cancer cells.
2012
Sorafenib, a multikinase inhibitor, recently received FDA approval for the treatment of advanced hepatocellular carcinoma (HCC). However, as the clinical application of sorafenib evolves, there is increasing interest in defining the mechanisms underlying its anti-tumor activity. Considering that this specific inhibitor could target unexpected molecules depending on the biologic context, a precise understanding of its mechanism of action could be critical to maximize its treatment efficacy, while minimizing adverse effects. Two human HCC cell lines (HepG2 and Huh7), carrying different biological and genetic characteristics, were used in this study to examine the intracellular events leading …
BIBF 1120/ nintedanib : a new triple angiokinase inhibitor-directed therapy in patients with non-small cell lung cancer.
2013
Abstract: Introduction: Several new targeted agents with anti-angiogenic properties have been developed recently, including vandetanib, sunitinib, sorafenib, bevacizumab and others. Tumor development, progression, metastasis are strongly linked to angiogenesis. Targeted agents like bevacizumab, a monoclonal antibody which targets VEGF, have been fully developed in several solid tumors. These new agents strongly advocate that targeting angiogenesis is one of the best approaches for cancer therapy. Areas covered: Those agents that target additional pro-angiogenic intracellular signaling pathways beyond VEGF signaling have also the potential to contribute to anticancer therapies. The authors p…
3,4-Diarylmaleimides Effectively Inhibit Proliferation of FLT3-ITD-Positive Leukemic Cells, Induce Apoptosis and Show Additive Effects in Combination…
2007
Abstract Internal tandem duplication (ITD) mutations of FLT3 are present in leukemic blasts of approximately 30% of AML patients. ITD-mutations of FLT3 confer a worse prognosis and decreased overall survival. Therefore, FLT3-tyrosine kinase is considered an attractive drug target in AML and several FLT3-tyrosine kinase inhibitors (TKIs) are currently being tested in clinical trials (CEP701, MLN518, Sorafenib, PKC412). However, using these drugs as monotherapy, against the setting of remarkable efficacy has emerged the problem of short duration of remission indicating rapid development of secondary resistance. In addition, up to 30% of patients may show primary resistance to currently availa…
Abstract 1902: Enrichment of putative cancer stem cells during anti-angiogenic therapies promotes relapse formation in hepatocellular carcinoma
2017
Abstract Background and Aims: Activation of neo-angiogenic processes in hepatocellular carcinoma (HCC) during disease progression is frequently associated with poor clinical outcome. Consequently, inhibition of neo-angiogenesis is an effective treatment strategy for advanced HCC. However, development of chemoresistance is observed in the majority of patients. Compelling evidence suggest that cancer stem cells (CSCs) may contribute to the acquisition of resistant properties in many solid tumors, but their exact role in this process for HCC remains to be defined. Here, we evaluate the importance of CSCs in the development of resistance and relapse formation after exposure to different anti-an…
Visceral fat area as a new independent predictive factor of survival in patients with metastatic renal cell carcinoma treated with antiangiogenic age…
2011
Abstract Purpose. A better identification of patients who are more likely to benefit from vascular endothelial growth factor–targeted therapy is warranted in metastatic renal cell carcinoma (mRCC). As adipose tissue releases angiogenic factors, we determined whether parameters such as visceral fat area (VFA) were associated with outcome in these patients. Experimental Design. In 113 patients with mRCC who received antiangiogenic agents (bevacizumab, sunitinib, or sorafenib) (n = 64) or cytokines (n = 49) as first-line treatment, we used computed tomography to measure VFA and subcutaneous fat area (SFA). We evaluated associations linking body mass index (BMI), SFA, and VFA to time to progres…
Noninvasive Flap Preconditioning by Foam-Mediated External Suction Improves the Survival of Fasciocutaneous Axial-Pattern Flaps in a Type 2 Diabetic …
2018
Background Advances in reconstructive surgery are leading to an increased number of flaps at risk for ischemic necrosis, because of either intrinsic (e.g., larger flap size) or extrinsic (e.g., diabetes) factors. Methods to preoperatively improve flap vascularity and limit postoperative ischemia are lacking. Noninvasive suction, using either a macrodeformational silicone cup interface (external volume expansion) or a microdeformational polyurethane foam interface (foam-mediated external volume expansion), has been shown to induce angiogenesis in tissues. The authors investigated whether the preoperative use of external volume expansion/foam-mediated external volume expansion improves flap s…
Type-II transmembrane prolyl dipeptidases and matrix metalloproteinases in membrane vesicles of active endothelial cells.
2006
Conclusions: Endothelia cells in sparse culture are migratory and increase the production of gelatinases of serine- and metallo-classes in membrane vesicles. Collectively, proteases associated with membrane vesicles degrade extracellular matrix components including type-I and type-IV collagens, laminin and fibronectin. Inhibitor studies suggest the existence of small gelatinases that were derived from these serine- and metallo-proteases. Thus, further studies are warranted to demonstrate the cooperative action of metallo- and serine proteases on cell surfaces and in extracellular vesicles during endothelial cell migration in 3D collagenous matrices, and potential proteolytic activation mech…
Synthesis of Fluorinated and Nonfluorinated Tebufenpyrad Analogues for the Study of Anti-angiogenesis MOA
2014
In this contribution we report the synthesis of fluorinated and nonfluorinated tebufenpyrad analogues to explore potential druglike properties through the phenotypic screening as part of the Lilly Open Innovation Drug Discovery (OIDD) program.
The Role of Oxidative Stress in the Response of Endothelial Cells to Metals
2012
The involvement of endothelial cells in inflammation and blood vessel formation (angiogenesis) makes them important for the integration of metal implants. Metal degradation products can, however, influence these processes, possibly leading to ineffective wound healing, prolonged inflammation and eventually aseptic loosening of the implant. Different metal degradation processes have been shown to lead to ROS formation. Oxidative stress, therefore, can mediate the reactions of the human body to the implant. While the response of endothelial cells to oxidative stress has been well studied, the effects of ROS produced as the result of metal degradation have not been addressed as yet. Therefore,…