Imaging of αvβ3 Expression by a Bifunctional Chimeric RGD Peptide not Cross-Reacting with αvβ5

Zannetti, Antonella; Vecchio, Silvana Del; Iommelli, Francesca; Gatto, Annarita Del; Luca, Stefania De; Zaccaro, Laura; Papaccioli, Angela; Sommella, Jvana; Panico, Mariarosaria; Speranza, Antonio; Grieco, Paolo; Novellino, Ettore; Saviano, Michele; Pedone, Carlo; Salvatore, Marco

doi:10.1158/1078-0432.ccr-08-3270

Cited by 42 publications

(71 citation statements)

References 38 publications

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“…64 Imaging ligands for α v β 3 are available, and have been used in PET studies in animal models of cancer. 65 The inverse correlation between α v β 3 expression and endothelial permeability suggests that this molecule is downregulated in conditions of microvascular leak, and that examining its expression in patients with sepsis would be of great interest.…”

Section: Endothelial Activationmentioning

confidence: 99%

Imaging in sepsis-associated encephalopathy—insights and opportunities

2013

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Sepsis-associated encephalopathy (SAE) refers to a clinical spectrum of acute neurological dysfunction that arises in the context of sepsis. Although the pathophysiology of SAE is incompletely understood, it is thought to involve endothelial activation, blood-brain barrier leakage, inflammatory cell migration, and neuronal loss with neurotransmitter imbalance. SAE is associated with a high risk of mortality. Imaging studies using MRI and CT have demonstrated changes in the brains of patients with SAE that are also seen in disorders such as stroke. Next-generation imaging techniques such as magnetic resonance spectroscopy, diffusion tensor imaging and PET, as well as experimental imaging modalities, provide options for early identification of patients with SAE, and could aid in identification of pathophysiological processes that represent possible therapeutic targets. In this Review, we explore the recent literature on imaging in SAE, relating the findings of these studies to pathological data and experimental studies to obtain insights into the pathophysiology of sepsis-associated neurological dysfunction. Furthermore, we suggest how novel imaging technologies can be used for early-stage proof-of-concept and proof-of-mechanism translational studies, which may help to improve diagnosis in SAE.

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Section: Endothelial Activationmentioning

confidence: 99%

Imaging in sepsis-associated encephalopathy—insights and opportunities

2013

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“…16 RGD peptide conjugated with nanomaterials enabled tracing of glioma in a photoinduced electron transfer imaging system. [17][18][19] We found that RGD and c(RGDfC) polyionic complex micelles, but not vehicle control or polyionic complexes, induced apoptosis of human glioma cells in vitro.…”

Section: Discussionmentioning

confidence: 87%

Targeted therapy for glioma using cyclic RGD-entrapped polyionic complex nanomicelles

Liu¹

2012

IJN

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Background:The purpose of this study was to test the efficacy of cyclic Arg-Gly-Asp (RGD) peptide conjugated with polyionic complex nanomicelles as targeted therapy for glioma. Methods: A stable cyclic RGD polyionic complex nanostructure, ie, a c(RGDfC) polyionic complex micelle, was synthesized and its biocompatibility with cultured neurons was assessed using a cell viability assay. Targeted binding to cultured glioma cells was evaluated by the CdTe quantum dot marking technique and a cell viability assay. The inhibitory effect of the nanomicelles against glioma cells was also evaluated, and their targeted migration into rat brain glioma cells and apoptotic effects were traced by the CdTe quantum dot marking and immunohistochemical staining. Results: c(RGDfC) polyionic complex micelles did not affect the growth of neurons but bonded selectively to and inhibited proliferation of glioma cells in vitro. When tested in vivo, the micelles migrated into glioma cells, inducing apoptosis in the rat brain. Conclusion:The c(RGDfC) polyionic complex micelle is an effective targeted therapy against glioma.

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“…Levels of αvβ3, αvβ5, αIIbβ3 and α5β1 integrins were determined by fluorescence-activated cell sorting (BD FACSAria II, Franklin Lakes, NJ, USA) [29]. Briefly, selected cell lines (5 × 10 5 ) were incubated with FITC-conjugated mouse antibodies LM609 (Merck KGaA, Darmstadt, Germany), P1F6 (Merck KGaA) and A2A9/6 (Santa Cruz, Dallas, TX, USA) recognizing ανβ3, ανβ5 and αIIbβ3 integrins, respectively, for 1 h at 4 °C in the dark.…”

Section: Methodsmentioning

confidence: 99%

Neutrophil Extracellular Traps as an Adhesion Substrate for Different Tumor Cells Expressing RGD-Binding Integrins

Monti

Rosa

Iommelli

et al. 2018

IJMS

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Neutrophil extracellular traps (NETs), in addition to their function as a host defense mechanism, play a relevant role in thrombus formation and metastatic dissemination of cancer cells. Here we screened different cancer cell lines endogenously expressing a variety of integrins for their ability to bind to NETs. To this end, we used NETs isolated from neutrophil-like cells as a substrate for adhesion assays of HT1080, U-87 MG, H1975, DU 145, PC-3 and A-431 cells. Levels of α5, αIIb, αv, β1, β3 and β5 chains were determined by western blot analysis in all cell lines and levels of whole integrins on the plasma membrane were assessed by fluorescence-activated cell sorting (FACS) analysis. We found that high levels of α5β1, αvβ3 and αvβ5 enhance cell adhesion to NETs, whereas low expression of α5β1 prevents cell attachment to NETs. Excess of cyclic RGD peptide inhibited cell adhesion to NETs by competing with fibronectin within NETs. The maximal reduction of such adhesion was similar to that obtained by DNase 1 treatment causing DNA degradation. Our findings indicate that NETs from neutrophil-like cells may be used as a substrate for large screening of the adhesion properties of cancer cells expressing a variety of RGD-binding integrins.

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Imaging of αvβ3 Expression by a Bifunctional Chimeric RGD Peptide not Cross-Reacting with αvβ5

Cited by 42 publications

References 38 publications

Imaging in sepsis-associated encephalopathy—insights and opportunities

Imaging in sepsis-associated encephalopathy—insights and opportunities

Targeted therapy for glioma using cyclic RGD-entrapped polyionic complex nanomicelles

Neutrophil Extracellular Traps as an Adhesion Substrate for Different Tumor Cells Expressing RGD-Binding Integrins

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