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Nate Larson, Sarah Roberts, Abhijit Ray, Brandon Buckway, Darwin L Cheney, Hamidreza Ghandehari
HPMA copolymer-RGDfK (HPMA-RGDfK) conjugates bearing either aminohexylgeldanamycin (AHGDM) or docetaxel (DOC) were synthesized and characterized. In vitro stability and binding were evaluated. Cytotoxicity toward ovarian cancer cells was evaluated and the ability of the conjugates to induce cell death was assessed by combination index analysis. Conjugates bearing AHGDM were more stable and exhibited slower drug release than those bearing DOC. Both conjugates demonstrated the ability to bind to avb3 integrins...
December 2014: Macromolecular Bioscience
Gioel Gabrio Secco, Mara Sansa, Andrea Rognoni, Rosario Parisi, Rossella Fattori, Lidia Rossi, Maurizio Lazzero, Roberta Rolla, Giorgio Bellomo, Angelo Sante Bongo, Pierfrancesco Agostoni, Carlo Di Mario, Alessandro Lupi
BACKGROUND: Intracoronary Abciximab administration during primary percutaneous coronary intervention (pPCI) could offer theoretical advantages over the intravenous route. Besides antiplatelet effects, Abciximab can modulate inflammation via cross-reactivity with GPIIb/IIIa, avb3, and aMb2 receptors. The aim of our study was to assess whether the Abciximab administration route could influence its anti-inflammatory effects. METHODS: Eighty-nine consecutive ST elevation myocardial infarction patient candidates for pPCI were randomized to intracoronary (Group A-47 patients) or intravenous (Group B-42 patients) Abciximab bolus administration...
March 2015: Journal of Cardiovascular Medicine
Hye-Nam Son, Ju-Ock Nam, Soyoun Kim, In-San Kim
TGFBI, a transforming growth factor β-induced extracellular matrix protein, circulates at a level of ~300ng/ml in humans and modulates several integrin-mediated cellular functions. The protein contains an N-terminal EMI domain, four consecutive FAS1 domains, and the RGD motif. Each FAS1 domain and the RGD motif have been known to interact with avb3 integrin. Here, we found that the binding affinity (Kd) of TGFBI for αvβ3 integrin was approximately 3.8×10(-8)M, a value ~2300-fold higher than that of a single FAS1 domain, and demonstrated that this greater affinity was due to the cooperative action of the four FAS1 domains and the RGD motif...
October 2013: Biochimica et Biophysica Acta
Chun-Han Hou, Chih-Hsin Tang, Chin-Jung Hsu, Sheng-Mon Hou, Ju-Fang Liu
INTRODUCTION: Osteoarthritis (OA) is the most common degenerative joint disease that is involved in the degradation of articular cartilage. The exact etiology of OA is not completely understood. CCN4 is related to up-regulation in the cartilage of patients with osteoarthritis. Previous studies have shown that CCN4 might be associated with the pathogenesis of OA, but the exact signaling pathways in CCN4-mediated IL-6 expression in synovial fibroblasts (SF) are largely unknown. Therefore, we explored the intracellular signaling pathway involved in CCN4-induced IL-6 production in human synovial fibroblast cells...
2013: Arthritis Research & Therapy
Antonio Garcia-Gomez, Enrique M Ocio, Atanasio Pandiella, Jesús F San Miguel, Mercedes Garayoa
INTRODUCTION: The RAS/RAF/MEK/ERK signaling pathway plays an important role in osteoclast (OC) differentiation and survival mediated by macrophage-colony stimulating factor (M-CSF). Also, vascular endothelial growth factor (VEGF) may greatly influence OC formation and resorption through VEGFR1 and VEGFR2. RAF265 is a novel, orally bioavailable dual inhibitor of RAF kinase and VEGFR2. METHODS: Effect of RAF265 on osteoclastogenesis from peripheral blood mononuclear cells (PBMCs) and OC resorption on calcium-coated wells was assessed by appropriate in vitro assays...
February 2013: Investigational New Drugs
K Fukushima, K Tsukimori, D Li, T Takao, S Morokuma, K Kato, H Seki, S Takeda, S Matsumura, N Wake
Low level, antenatal exposure to dioxins is associated with low birth weight, which in turn is associated with long-term sequelae. We exposed the human extravillous cytotrophoblast (EVT) lines HTR-8/SV40 and TCL1 to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and assessed cell growth, invasion, and differentiation. TCDD had no effect on cell proliferation, invasion, or tube formation in Matrigel. The EVT-derived cells expressed a functional aryl hydrocarbon receptor protein; however, TCDD exposure did not alter expression levels of proteins involved in EVT differentiation in early pregnancy, including hypoxia-inducible factor 1A (HIF1A), vascular endothelial growth factor (VEGF), Integrin A1, A6, and AVB3...
June 2012: Human & Experimental Toxicology
Felix P Koch, Annette Wunsch, Christina Merkel, Thomas Ziebart, Andreas Pabst, Sareh Said Yekta, Marco Blessmann, Ralf Smeets
BACKGROUND: Bisphosphonates are therapeutics of bone diseases, such as Paget's disease, multiple myeloma or osteoclastic metastases. As a severe side effect the bisphosphonate induced osteonecrosis of the jaw (BONJ) often requires surgical treatment and is accompanied with a disturbed wound healing.Therefore, the influence on adhesion and migration of human osteoblasts (hOB) after bisphosphonate therapy has been investigated by morphologic as well as gene expression methods. METHODS: By a scratch wound experiment, which measures the reduction of defined cell layer gap, the morphology and migration ability of hOB was evaluated...
2011: Head & Face Medicine
L Zhu, G Niu, X Fang, X Chen
Angiogenesis, a course that new blood vessels grow from the existing vasculature, plays important roles both physiologically and pathologically. Angiogenesis can be switched on by growth factors secreted by tumor cells, and in turn supplies more oxygen and nutrition to the tumor. More and more preclinical studies and clinical trials have shown that inhibition of angiogenesis is an effective way to inhibit tumor growth, substantiating the development of anti-angiogenesis therapeutics. Imaging technologies accelerate the translation of preclinical research to the clinic...
June 2010: Quarterly Journal of Nuclear Medicine and Molecular Imaging
F C Gaertner, M Schwaiger, A J Beer
Angiogenesis, the formation of new blood vessels, is a key process in the growth of solid tumors. Thus this process could potentially be utilized for diagnosis of malignancies by molecular imaging on the one hand and for tumor treatment on the other hand. Imaging of angiogenesis has become increasingly important with the rising use of targeted antiangiogenic therapies, like bevacizumab (Avastin). Non-invasive assessment of angiogenic activity is in this respect interesting e.g. for response assessment of such targeted antiangiogenic therapies...
June 18, 2010: Quarterly Journal of Nuclear Medicine and Molecular Imaging
R Cesareo, C Napoletano, M Iozzino, B De Rosa, G Iarussi, M Scona, F Romitelli
The World Health Organization (WHO) declared osteoporosis "social disease". The present revision of the literature will focus on the recent acquisitions in bone pathophysiology and the efforts in the formulation of new molecules able to change successfully the course of the disease. Osteocyte cell is now thought to be the main biomechanical transducer of bones, able to release sclerostin that produces inhibition on osteosynthesis and on the other hand to release substances like nitrid oxide and prostaglandins that provide a stimulus to osteosynthesis through direct or indirect activation of osteoblasts...
September 2009: Minerva Endocrinologica
A E Semenova, I V Sergienko, S A Gabrusenko
Stimulatiion of coronary angiogenesis in patients with IHD appears to be one of perspective directions in contemporary cardiology. Therefore objective assessment of results with the help of instrumental methods of investigation is important. For assessment of the state of coronary vascular bed and myocardial perfusion in the clinic one can use coronarography, single photon emission computer tomography, positron emission tomography, magnetic resonance tomography, and contrast echocardiography. Novel techniques of visualization are elaborated at present with consideration of peculiarities of mechanisms and use of molecular markers of angiogenesis: visualization of integrin avb3, VEGF-receptors, visualization of activity of matrix metalloproteinases...
2008: Kardiologiia
Andras Czirok, Evan A Zamir, Andras Szabo, Charles D Little
Living organisms, from bacteria to vertebrates, are well known to generate sophisticated multicellular patterns. Numerous recent interdisciplinary studies have focused on the formation and regulation of these structures. Advances in automatized microscopy allow the time-resolved tracking of embryonic development at cellular resolution over an extended area covering most of the embryo. The resulting images yield simultaneous information on the motion of multiple tissue components-both cells and extracellular matrix (ECM) fibers...
2008: Current Topics in Developmental Biology
Dean J Kereiakes
The platelet glycoprotein (GP) IIb/IIIa inhibitors differ markedly in their pharmacokinetics, pharmacodynamics, and differential receptor affinities. Abciximab and the small-molecule GP IIb/IIIa inhibitors (eptifibatide, tirofiban) have separate, distinct binding sites on the GP IIb/IIIa receptor complex. The affinity of abciximab for the platelet GP IIb/IIIa integrin receptor, together with non-platelet-receptor mediated effects achieved through its affinity for the aVb3 and CD11b/18 receptors, most likely contribute to the clinical benefit associated with the use of abciximab as adjunctive pharmacotherapy during primary percutaneous coronary intervention for the treatment of ST-elevation acute myocardial infarction...
2006: Reviews in Cardiovascular Medicine
S A Mousa, F B Davis, S Mohamed, P J Davis, X Feng
AIM: Our laboratory has recently demonstrated the pro-angiogenesis effects of thyroid hormone in the chick chorioallantoic membrane model. METHODS: Generation of new blood vessels from existing vessels was promoted two- to three-fold by either L-thyroxine (T4) or 3,5,3'-triiodo-L-thyronine (T3) at total hormone concentrations of T7-T9 M. RESULTS: T4-agarose, a formulation of thyroid hormone that does not cross the cell membrane, produced a potent pro-angiogenesis effect comparable to that obtained with T3 or T4...
December 2006: International Angiology: a Journal of the International Union of Angiology
Kamal Chitkara, Kai Hogrefe, Mariuca Vasa-Nicotera, Neil Swanson, Anthony H Gershlick
OBJECTIVE: Stent thrombosis and in-stent restenosis remain problematic despite drug-eluting stents (DES), especially in diabetic patients and in those with small-vessel disease. Eptifibatide inhibits the platelet glycoprotein IIb/IIIa and smooth muscle cell (SMC) avb3 receptor, thus potentially influencing both thrombosis and proliferation. The aim of the present studies was to examine the absorption and elution characteristics of eptifibatide on polymer-coated stents and investigated their effect on SMC proliferation, platelet deposition and platelet aggregation in vitro...
September 2006: Journal of Invasive Cardiology
A Meyer, J Auernheimer, A Modlinger, H Kessler
Integrins constitute an important class of cell adhesion receptors responsible not only for cell-matrix adhesion but also for signaling bidirectionally across the membrane. Integrins are involved in many biological processes such as angiogenesis, thrombosis, inflammation, osteoporosis and cancer. Integrins thus play a key role in many severe human diseases. In this review we will describe recent research and development of RGD-containing integrin ligands for medical applications including drug design, radiolabeling, drug targeting, as well as biomaterial research...
2006: Current Pharmaceutical Design
Vinay Gupta, Weijun Wang, Barbara A Sosnowski, Florence M Hofman, Thomas C Chen
OBJECT: Adenovirus transduction in gene therapy is dependent on the expression of the coxsackie virus-adenovirus receptor (CAR) for initial binding and on the integrin receptors (avb3, avb5) for viral internalization. Low and variable expression of CAR may be responsible for the low transduction rates seen with native adenoviral vectors. The goal of this study was to demonstrate increased transduction efficiency by retargeting the adenovirus with a fibroblast growth factor (FGF) ligand, FGF-2...
2006: Neurosurgical Focus
David C Paik, Chenzhong Fu, Jahar Bhattacharya, M David Tilson
Pathogenesis of the abdominal aortic aneurysm has been attributed to neovascularization of the aortic wall. However, it is not clear whether angiogenesis persists in the aneurysm. In sections of aneurysms, we determined the immunohistochemical distributions of the avb3 integrin, tenascin and endothelial nitric oxide synthase (eNOS), which are markers respectively, of angiogenesis, matrix remodeling and vasoregulatory function. In addition, we used reverse transcription followed by in situ PCR, to determine the distribution of av mRNA...
December 31, 2004: Experimental & Molecular Medicine
M A Chellaiah, K A Hruska
In the studies reported here we demonstrate that osteopontin is secreted from the basolateral surfaces of osteoclasts where it binds to the avb3-integrin, suggesting that it may be an autocrine factor. Osteopontin stimulation of osteoclasts produced changes in cell shape by causing disruption of peripheral podosome structures and formation of actin filaments at the leading edge of the migrating osteoclasts. The latter was part of the assumption of a motile phenotype prior to cells reforming peripheral ring type podosome containing clear zones...
March 2003: Calcified Tissue International
Roberto Ria, Angelo Vacca, Domenico Ribatti, Francesco Di Raimondo, Francesca Merchionne, Franco Dammacco
BACKGROUND AND OBJECTIVES: In multiple myeloma (MM), the mechanisms used by plasma cells to invade locally and metastasize are thought to be similar to those developed by solid tumors and include cell proliferation and secretion of extracellular matrix (ECM) degrading enzymes following adhesion to ECM proteins. We studied these mechanisms in fresh bone marrow plasma cells of patients with MM after adhesion to the ECM proteins vitronectin (VN) and fibronectin (FN). DESIGN AND METHODS: The ability of bone marrow plasma cells to adhere to VN and FN and the consequent formation of focal adhesion plaques on the cell surface, their composition and phosphorylation of several signal transduction proteins, cell proliferation and secretion of matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) and urokinase-type plasminogen activator (uPA) were studied...
August 2002: Haematologica
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