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https://www.readbyqxmd.com/read/28523582/first-in-human-radiation-dosimetry-of-68-ga-nodaga-rgdyk
#1
Silvano Gnesin, Periklis Mitsakis, Francesco Cicone, Emmanuel Deshayes, Vincent Dunet, Augusto F Gallino, Marek Kosinski, Sébastien Baechler, Franz Buchegger, David Viertl, John O Prior
BACKGROUND: Integrin-targeting radiopharmaceuticals have potential broad applications, spanning from cancer theranostics to cardiovascular diseases. We have previously reported preclinical dosimetry results of (68)Ga-NODAGA-RGDyK in mice. This study presents the first human dosimetry of (68)Ga-NODAGA-RGDyK in the five consecutive patients included in a clinical imaging protocol of carotid atherosclerotic plaques. Five male patients underwent whole-body time-of-flight (TOF) PET/CT scans 10, 60 and 120 min after tracer injection (200 MBq)...
December 2017: EJNMMI Research
https://www.readbyqxmd.com/read/28518069/modification-and-functionalization-of-the-guanidine-group-by-tailor-made-precursors
#2
Tobias G Kapp, Maximilian Fottner, Horst Kessler
The guanidine group is one of the most important pharmacophoric groups in medicinal chemistry. The only amino acid carrying a guanidine group is arginine. In this article, an easy method for the modification of the guanidine group in peptidic ligands is provided, with an example of RGD-binding integrin ligands. It was recently demonstrated that the distinct modification of the guanidine group in these ligands allows for the selective modulation of the subtype (e.g., between the subtypes αv and α5). Moreover, a formerly unknown strategy for the functionalization via the guanidine group was demonstrated, and the synthetic approach is reviewed in this document...
April 27, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28514856/cell-adhesion-on-rgd-displaying-knottins-with-varying-number-of-tryptophan-amino-acids-to-tune-the-affinity-for-assembly-on-cucurbit-8-uril-surfaces
#3
Shrikrishnan Sankaran, Emanuela Cavatorta, Jurriaan Huskens, Pascal Jonkheijm
Cell adhesion is studied on multivalent knottins, displaying RGD ligands with high affinity for integrin receptors, that are assembled on CB[8]-methylviologen-modified surfaces. The multivalency in the knottins stems from the number of tryptophan amino acid moieties, between 0 and 4, that can form a heteroternary complex with cucurbit[8]uril (CB[8]) and surface-tethered methylviologen (MV2+). The binding affinity of the knottins with CB[8] and MV2+ surfaces was evaluated using surface plasmon resonance spectroscopy...
May 18, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/28514760/clinical-study-of-99mtc-3p-rgd2-peptide-imaging-in-osteolytic-bone-metastasis
#4
Guoqiang Shao, Wei Gu, Muhong Guo, Shiming Zang, Jinjing Fu, Shuang Liu, Feng Wang, Zizheng Wang
OBJECTIVE: To investigate the value of integrin αvβ3 targeted imaging with 99mTc-HYNIC-PEG4-E[PEG4-c(RGDfk)]2 (99mTc-3P-RGD2) as a radiotracer in dectecting osteolytic bone metastases. METHODS: This is a retrospective study involving a cohort of 69 consecutive patients including 59 with lung cancer and 10 with other cancers. Patients were required to receive whole body scan (WBS) and regional SPECT/CT imaging with 99mTc-3P-RGD2 (RGD imaging) and 99mTc-MDP (MDP imaging) as a radiotracer successively within days...
April 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28513838/the-emerging-role-of-npnt-in-tissue-injury-repair-and-bone-homeostasis
#5
REVIEW
Youqiang Sun, Vincent Kuek, Heng Qiu, Jennifer Tickner, Leilei Chen, Haibin Wang, Wei He, Jiake Xu
Nephronectin (NPNT), a highly conserved extracellular matrix protein, plays an important role in regulating cell adhesion, differentiation, spreading and survival. NPNT protein belongs to epidermal growth factor (EGF)-like superfamily and exhibits several common structural determinants; including EGF-like repeat domains, MAM domain (Meprin, A5 Protein, and Receptor Protein-Tyrosine Phosphatase µ), RGD motif (Arg-Gly-Asp) and a coiled-coil domain. It regulates integrins-mediated signaling pathways via the interaction of its RGD motif with integrin α8β1...
May 17, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28508555/laminin-and-collagen-iv-inclusion-in-immunoisolating-microcapsules-reduces-cytokine-mediated-cell-death-in-human-pancreatic-islets
#6
Alberto Llacua, Bart J de Haan, Paul de Vos
Extracellular matrix (ECM) molecules have several functions in pancreatic islets including provision of mechanical support and prevention of cytotoxicity during inflammation. During islet isolation, ECM-connections are damaged and are not restored after encapsulation and transplantation. Inclusion of specific combinations of collagen type IV and laminins in immunoisolating capsules can enhance survival of pancreatic islets. Here we investigated whether ECM can also enhance survival and lower susceptibility of human islets to cytokine-mediated cytotoxicity...
May 16, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28507934/the-challenges-of-recombinant-endostatin-in-clinical-application-focus-on-the-different-expression-systems-and-molecular-bioengineering
#7
REVIEW
Abbas Mohajeri, Sarvin Sanaei, Farhad Kiafar, Amir Fattahi, Majid Khalili, Nosratollah Zarghami
Angiogenesis plays an essential role in rapid growing and metastasis of the tumors. Inhibition of angiogenesis is a putative strategy for cancer therapy. Endostatin (Es) is an attractive anti-angiogenesis protein with some clinical application challenges including; short half-life, instability in serum and requirement to high dosage. Therefore, production of recombinant endostatin (rEs) is necessary in large scale. The production of rEs is difficult because of its structural properties and is high-cost. Therefore, this review focused on the different expression systems that involved in rEs production including; mammalian, baculovirus, yeast, and Escherichia coli (E...
April 2017: Advanced Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28505596/engineered-hydrogels-increase-the-post-transplantation-survival-of-encapsulated-hesc-derived-midbrain-dopaminergic-neurons
#8
Maroof M Adil, Tandis Vazin, Badriprasad Ananthanarayanan, Gonçalo M C Rodrigues, Antara T Rao, Rishikesh U Kulkarni, Evan W Miller, Sanjay Kumar, David V Schaffer
Cell replacement therapies have broad biomedical potential; however, low cell survival and poor functional integration post-transplantation are major hurdles that hamper clinical benefit. For example, following striatal transplantation of midbrain dopaminergic (mDA) neurons for the treatment of Parkinson's disease (PD), only 1-5% of the neurons typically survive in preclinical models and in clinical trials. In general, resource-intensive generation and implantation of larger numbers of cells are used to compensate for the low post-transplantation cell-survival...
May 5, 2017: Biomaterials
https://www.readbyqxmd.com/read/28502767/modulating-angiogenesis-with-integrin-targeted-nanomedicines
#9
Aroa Duro-Castano, Elena Gallon, Caitlin Decker, María J Vicent
Targeting angiogenesis-related pathologies, which include tumorigenesis and metastatic processes, has become an attractive strategy for the development of efficient guided nanomedicines. In this respect, integrins are cell-adhesion molecules involved in angiogenesis signaling pathways and are overexpressed in many angiogenic processes. Therefore, they represent specific biomarkers not only to monitor disease progression but also to rationally design targeted nanomedicines. Arginine-glycine-aspartic (RGD) containing peptides that bind to specific integrins have been widely utilized to provide ligand-mediated targeting capabilities to small molecules, peptides, proteins, and antibodies, as well as to drug/imaging agent-containing nanomedicines, with the final aim of maximizing their therapeutic index...
May 12, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/28499870/fibronectin-on-extracellular-vesicles-from-microvascular-endothelial-cells-is-involved-in-the-vesicle-uptake-into-oligodendrocyte-precursor-cells
#10
Sho Osawa, Masashi Kurachi, Hanako Yamamoto, Yuhei Yoshimoto, Yasuki Ishizaki
We previously reported transplantation of brain microvascular endothelial cells (MVECs) into cerebral white matter infarction model improved the animal's behavioral outcome by increasing the number of oligodendrocyte precursor cells (OPCs). We also revealed extracellular vesicles (EVs) derived from MVECs promoted survival and proliferation of OPCs in vitro. In this study, we investigated the mechanism how EVs derived from MVECs contribute to OPC survival and proliferation. Protein mass spectrometry and enzyme-linked immunosorbent assay revealed fibronectin was abundant on the surface of EVs from MVECs...
May 9, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28498874/soluble-bone-derived-osteopontin-promotes-migration-and-stem-like-behavior-of-breast-cancer-cells
#11
Graciella M Pio, Ying Xia, Matthew M Piaseczny, Jenny E Chu, Alison L Allan
Breast cancer is a leading cause of cancer death in women, with the majority of these deaths caused by metastasis to distant organs. The most common site of breast cancer metastasis is the bone, which has been shown to provide a rich microenvironment that supports the migration and growth of breast cancer cells. Additionally, growing evidence suggests that breast cancer cells that do successfully metastasize have a stem-like phenotype including high activity of aldehyde dehydrogenase (ALDH) and/or a CD44+CD24- phenotype...
2017: PloS One
https://www.readbyqxmd.com/read/28497694/stapled-rgd-peptide-enables-glioma-targeted-drug-delivery-by-overcoming-multiple-barriers
#12
Huitong Ruan, Xishan Chen, Cao Xie, Beibei Li, Man Ying, Yu Liu, Mingfei Zhang, Xuesai Zhang, Changyou Zhan, Wuyuan Lu, Weiyue Lu
Malignant glioma, the most frequent and aggressive central nervous system (CNS) tumor, severely threatens human health. One reason for its poor prognosis and short survival is the presence of the blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB), which restrict the penetration of therapeutics into the brain at different stages of glioma. Herein, inspired by the peptide stapling technique, we designed a cyclic RGD ligand via an all-hydrocarbon staple (stapled RGD, sRGD) to facilitate BBB penetration while retaining the capacity of BBTB penetration and targeting ability to glioma cells...
May 18, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28492301/high-affinity-rgd-knottin-peptide-as-a-new-tool-for-rapid-evaluation-of-the-binding-strength-of-unlabeled-rgd-peptides-to-%C3%AE-v%C3%AE-3-%C3%AE-v%C3%AE-5-and-%C3%AE-5%C3%AE-1-integrin-receptors
#13
Dominik Bernhagen, Laura De Laporte, Peter Timmerman
We describe a highly sensitive competition ELISA to measure integrin-binding of RGD-peptides in high-throughput without using cells, ECM-proteins or antibodies. The assay measures (non-labeled) RGD-peptides' ability to inhibit binding of a biotinylated 'knottin'-RGD peptide to surface-immobilized integrins, and thus enables quantification of the binding strength of high-, medium- and low-affinity RGD-binders. We introduced the biotinylated knottin-RGD peptide instead of biotinylated cyclo[RGDfK] (as reported by Piras et al...
May 11, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28489328/induction-of-chondrogenic-differentiation-of-human-mesenchymal-stem-cells-by-biomimetic-gold-nanoparticles-with-tunable-rgd-density
#14
Jingchao Li, Xiaomeng Li, Jing Zhang, Naoki Kawazoe, Guoping Chen
Nanostructured materials have drawn a broad attention for their applications in biomedical fields. Ligand-modified nanomaterials can well mimic the dynamic extracellular matrix (ECM) microenvironments to regulate cell functions and fates. Herein, ECM mimetic gold nanoparticles (Au NPs) with tunable surface arginine-glycine-aspartate (RGD) density are designed and synthesized to induce the chondrogenic differentiation of human mesenchymal stem cells (hMSCs). The biomimetic Au NPs with an average size of 40 nm shows good biocompatibility without affecting the cell proliferation in the studied concentration range...
May 10, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28482232/control-of-angiogenesis-and-host-response-by-modulating-the-cell-adhesion-properties-of-an-elastin-like-recombinamer-based-hydrogel
#15
Sebastian Manuel Staubli, Giulia Cerino, Israel Gonzalez De Torre, Matilde Alonso, Daniel Oertli, Friedrich Eckstein, Katharina Glatz, José Carlos Rodríguez Cabello, Anna Marsano
The control of the in vivo vascularization of engineered tissue substitutes is essential in order to obtain either a rapid induction or a complete inhibition of the process (e.g. in muscles and hyaline-cartilage, respectively). Among the several polymers available, Elastin-Like Recombinamers (ELR)-based hydrogel stands out as a promising material for tissue engineering thanks to its viscoelastic properties, non-toxicity, and non-immunogenicity. In this study, we hypothesized that varying the cell adhesion properties of ELR-hydrogels could modulate the high angiogenic potential of adipose tissue-derived stromal vascular fraction (SVF) cells, predominantly composed of endothelial/mural and mesenchymal cells...
April 28, 2017: Biomaterials
https://www.readbyqxmd.com/read/28480325/the-sequence-of-delta24-rgd-and-tmz-administration-in-malignant-glioma-affects-the-role-of-cd8-t-cell-anti-tumor-activity
#16
Anne Kleijn, Wouter van den Bossche, Erik S Haefner, Zineb Belcaid, Chantal Burghoorn-Maas, Jenneke J Kloezeman, Suzan D Pas, Sieger Leenstra, Reno Debets, Jeroen de Vrij, Clemens M F Dirven, Martine L M Lamfers
The conditionally replicating oncolytic adenovirus Delta24-RGD (Ad) is currently under investigation in clinical trials for glioblastoma, including in combination with temozolomide (TMZ), the standard chemotherapy for this tumor. Previously, we showed that the efficacy of Delta24-RGD in a murine model is primarily dependent on the virus-induced anti-tumor immune response. As observed with most chemotherapies, TMZ has pronounced immune-modulating effects. Here, we studied the combined effects of these treatments in a murine glioma model...
June 16, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/28473400/integrin-targeted-cancer-immunotherapy-elicits-protective-adaptive-immune-responses
#17
Byron H Kwan, Eric F Zhu, Alice Tzeng, Harun R Sugito, Ahmed A Eltahir, Botong Ma, Mary K Delaney, Patrick A Murphy, Monique J Kauke, Alessandro Angelini, Noor Momin, Naveen K Mehta, Alecia M Maragh, Richard O Hynes, Glenn Dranoff, Jennifer R Cochran, K Dane Wittrup
Certain RGD-binding integrins are required for cell adhesion, migration, and proliferation and are overexpressed in most tumors, making them attractive therapeutic targets. However, multiple integrin antagonist drug candidates have failed to show efficacy in cancer clinical trials. In this work, we instead exploit these integrins as a target for antibody Fc effector functions in the context of cancer immunotherapy. By combining administration of an engineered mouse serum albumin/IL-2 fusion with an Fc fusion to an integrin-binding peptide (2...
May 4, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28471202/-use-of-porous-hydrogel-as-a-3d-scaffold-for-the-growth-of-leukemic-b-lymphocytes
#18
R Studená, D Horák, J Baloun, Z Plichta, Š Pospíšilová
BACKGROUND: Primary human B cells chronic lymphocytic leukemia undergoes apoptosis, from which they can be rescued by contact with stromal cells or by the addition of specific soluble factor, when cultured in vitro. For research purposes of the behavior of CLL cells we created 3D in vitro model in which we simulated appropriate microenvironment for CLL cells to allow study the mechanism of survival of these cells in long-term cultivation. MATERIAL AND METHODS: Our aim was the scaffold structure to be geometrically similar to the 3D morphology of supporting bone marrow tissue in a trabecular bone; the 3D scaffold was also designed to conform to biocompatibility, sufficiently large surface area for cell attachment, high porosity for cell migration, proliferation and transport of nutrients...
2017: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/28464225/self-assembly-hydrogels-as-multifunctional-drug-delivery-of-paclitaxel-for-synergistic-tumour-targeting-and-biocompatibility-in-vitro-and-in-vivo
#19
Chang Shu, Eboka M B Sabi-Mouka, Xiaoliang Wang, Li Ding
OBJECTIVES: In this work, we designed the self-assembly peptide hydrogels to multiply therapeutic agents for improving anticancer effect and lowering adverse reaction of paclitaxel (PTX). METHODS: The folate (FA)-peptide-PTX hydrogels consist of self-assemble peptide hydrogel as nanoscale carrier, FA and RGD peptide as targeting moieties and paclitaxel as anticancer drug. The properties of hydrogels, such as morphology, size distribution, zeta potential and rheology, were investigated...
May 2, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/28462989/developing-targeted-hybrid-imaging-probes-by-chelator-scaffolding
#20
Dominik Summer, Leo Grossrubatscher, Milos Petrik, Tereza Michalcikova, Zbynek Novy, Christine Rangger, Maximilian Klingler, Elisabeth von Guggenberg, Roland Haubner, Piriya Kaeopookum, Hubertus Haas, Clemens Decristoforo
Positron emission tomography (PET) as well as optical imaging (OI) with peptide receptor targeting probes have proven their value for oncological applications but also show restrictions depending on the clinical field of interest. Therefore the combination of both methods, particularly in a single molecule, could improve versatility in clinical routine. This proof of principle study aims to show that a chelator, Fusarinine C (FSC), can be utilized as scaffold for novel dimeric dual-modality imaging agents. Two targeting vectors (a minigastrin analogue (MG11) targeting cholecystokinin-2 receptor overexpression (CCK2R) or integrin V3 targeting cyclic pentapeptides (RGD)) and a near-infrared fluorophore (Sulfo-Cyanine7) were conjugated to FSC...
May 2, 2017: Bioconjugate Chemistry
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