Home About us Contact
|
Home About us Contact | ||
|
|
||
Angiogenic Inhibitors (angiogenic + inhibitor)
Selected AbstractsUltrasound assessment of short-term ocular vascular effects of intravitreal injection of bevacizumab (Avastin®) in neovascular age-related macular degenerationACTA OPHTHALMOLOGICA, Issue 6 2010Philippe Bonnin Acta Ophthalmol. 2010: 88: 641,645 Abstract. Purpose:, Angiogenic inhibitors, alone or combined with other therapies, are believed to represent a promising treatment for neovascularization in age-related macular degeneration (wet AMD). They can maintain or improve visual acuity (VA), at least for the first 2 years. However, evolution to retinal atrophy cannot be ruled out and it may be useful to assess the effects of antiangiogenic therapy on retinal and choroidal circulation. Methods:, We carried out a pilot study in 15 patients with wet AMD. Time-averaged mean blood flow velocities (BFVs) in the central retinal, temporal posterior ciliary and ophthalmic arteries (CRA, TPCA and OA) were measured by ultrasound imaging before and 4 weeks after a single intravitreal injection of 1.25 mg bevacizumab in 0.05 ml. Patients underwent two ophthalmic examinations, before and 4 weeks after injection, including VA measurement and optical coherence tomography (OCT3) examination. Results:, In treated eyes, bevacizumab injection was followed by a significant improvement in VA (from 20/125 to 20/80; p = 0.0214), and a decrease in mean central macular thickness (from 392 ± 96 ,m to 271 ± 50 ,m; p = 0.0038). Mean BFV decreased by 10% in the CRA (p = 0.0226), 20% in the TPCA (p = 0.0026) and 20% in the OA (p = 0.0003). No effect was observed in fellow eyes. Conclusions:, Intravitreal bevacizumab acutely improved VA and reduced central macular thickness in wet AMD. Ultrasound imaging revealed that BFVs decreased in all retrobulbar arteries, suggesting that after local diffusion, bevacizumab exerts a short-term regional effect. Bevacizumab might therefore induce hypoperfusion of the whole eye, which may correspond to a vascular side-effect. [source] Angiostatin K1-3 induces E-selectin via AP1 and Ets1: a mediator for anti-angiogenic action of K1-3JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 11 2008Y.-H. CHEN Summary.,Background:,Angiostatin, a circulating angiogenic inhibitor, is an internal fragment of plasminogen and consists of several isoforms, K1-3 included. We previously showed that K1-3 was the most potent angiostatin to induce E-selectin mRNA expression. The purpose of this study was to identify the mechanism responsible for K1-3-induced E-selectin expression and investigate the role of E-selectin in the anti-angiogenic action of K1-3. Methods and results:,Quantitative real time RT-PCR and Western blotting analyses confirmed a time-dependent increase of E-selectin mRNA and protein induced by K1-3. Subcellular fractionation and immunofluorescence microscopy showed the co-localization of K1-3-induced E-selectin with caveolin 1 (Cav1) in lipid rafts in which E-selectin may behave as a signaling receptor. Promoter-driven reporter assays and site-directed mutagenesis showed that K1-3 induced E-selectin expression via promoter activation and AP1 and Ets-1 binding sites in the proximal E-selectin promoter were required for E-selectin induction. The in vivo binding of both protein complexes to the proximal promoter was confirmed by chromatin immunoprecipitation (ChIP). Although K1-3 induced the activation of ERK1/2 and JNK, only repression of JNK activation attenuated the induction of E-selectin by K1-3. A modulatory role of E-selectin in the anti-angiogenic action of K1-3 was manifested by both overexpression and knockdown of E-selectin followed by cell proliferation assay. Conclusions:,We show that K1-3 induced E-selectin expression via AP1 and Ets-1 binding to the proximal E-selectin promoter (,356/+1), which was positively mediated by JNK activation. Our findings also demonstrate E-selectin as a novel target for the anti-angiogenic therapy. [source] Review article: future therapies for management of metastatic gastroenteropancreatic neuroendocrine tumoursALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 11 2009R. SRIRAJASKANTHAN Summary Background, Gastroenteropancreatic neuroendocrine tumours (GEP NETs) are relatively uncommon tumours that occur anywhere within the gastrointestinal tract. The prevalence of GEP NETs is estimated to be 35 per 100 000 population. Patients often present with metastatic disease and consequently, palliative treatments form the mainstay of therapy. Aim, To review the current and novel therapeutic options for management of GEP NETs. Methods, Searches for all studies related to GEP NETs, NETs and carcinoid tumours in Medline and abstracts from international meetings. Results, Somatostatin analogues remain the first line therapy for management of symptoms of GEP NETs and may have anti-proliferative action. New somatostatin analogues with different somatostatin receptor affinity have been developed. Radionuclide peptide receptor therapy is established in patients with positive somatostatin scintigraphy. A number of new agents and targeted therapies are currently being evaluated in a phase I and II studies and these include angiogenic inhibitors, mammalian target of rapamycin inhibitors and immune therapies. Conclusions, A number of nonsurgical therapies are available for management of gastroenteropancreatic neuroendocrine tumours. It is hoped, the development of some of these promising novel therapies will expand the therapeutic armamentarium. [source] Analysis of optimal controls for a mathematical model of tumour anti-angiogenesisOPTIMAL CONTROL APPLICATIONS AND METHODS, Issue 1 2008U. Ledzewicz Abstract Anti-angiogenic therapy is a novel treatment approach for cancer that aims at preventing a tumour from developing its own blood supply system that it needs for growth. In this paper we consider a mathematical model where the endogenous stimulation term in the dynamics is taken proportional to the number of endothelial cells. This system is an example from a class of mathematical models for anti-angiogenic treatment that were derived from a biologically validated model by Hahnfeldt, Panigrahy, Folkman and Hlatky. The problem how to schedule a given amount of angiogenic inhibitors to achieve a maximum reduction in the primary cancer volume is considered as an optimal control problem and it is shown that optimal controls are bang-bang of the type 0a0 with 0 denoting a trajectory corresponding to no treatment and a a trajectory with treatment at maximum dose along that all inhibitors are being exhausted. Copyright © 2007 John Wiley & Sons, Ltd. [source] | ||||||||||