Search results for " Targeting"

STRATEGIE DI DIREZIONAMENTO ALL’EPATOCARCINOMA DI FARMACI ANTITUMORALI MEDIANTE SISTEMI NANOPARTICELLARI E DI VISUALIZZAZIONE IN CELLULE TUMORALI DEL…

Lo scopo di questo lavoro di tesi è stato quello di realizzare nuovi sistemi nanoparticellari per il direzionamento di farmaci o di agenti per l’imaging, potenzialmente utilizzabili per la terapia e/o per la diagnosi dell’epatocarcinoma (HCC), in particolare per quelle forme caratterizzate dall’overespressione del recettore di membrana degli epatociti ASGP-R o del recettore mitocondriale TSPO. In particolare, nel capitolo 2 sono state descritte la sintesi, la caratterizzazione chimico fisica, la capacità di internalizzazione cellulare e l’efficacia antitumorale di un nuovo sistema nanoparticellare, costituito da un dendrimero a struttura poli-amido-aminica (PAMAM) di quarta generazione, opp…

Death receptors as targets in cancer

2013

Anti-tumour therapies based on the use PARAs (pro-apoptotic receptor agonists), including TRAIL (TNF-Related Apoptosis inducing Ligand) or monoclonal antibodies targeting TRAIL-R1 or TRAIL-R2, have been disappointing so far, despite clear evidence of clinical activity and lack of adverse events for the vast majority of these compounds, whether combined or not with conventional or targeted anti-cancer therapies. This brief review aims at discussing the possible reasons for the lack of apparent success of these therapeutic approaches and at providing hints in order to rationally design optimal protocols based on our current understanding of TRAIL signalling regulation or resistance for future…

in vitro biological evaluation of folate-functionalized block copolymer micelles for selective anti-cancer drug delivery.

2008

The main objective of this study was to evaluate the ability of folic acid-functionalized diblock copolymer micelles to improve the delivery and uptake of two poorly water-soluble anti-tumor drugs, tamoxifen and paclitaxel, to cancer cells through folate receptor targeting. The diblock copolymer used in this study comprised a hydrophilic poly[2-(methacryloyloxy)ethyl phosphorylcholine] (MPC) block, carrying at the chain end the folate targeting moiety, and a pH-sensitive hydrophobic poly[2-(diisopropylamino)ethyl methacrylate] (DPA) block (FA-MPC-DPA). The drug-loading capacities of tamoxifen- and paclitaxel-loaded micelles were determined by high performance liquid chromatography and the m…

Therapeutic targeting of apoptotic pathways in cancer.

2006

Programmed cell death (apoptosis) is a key tumor suppressor mechanism. Consequently, most if not all cancers develop mechanisms to abolish or circumvent this genetic program. Besides enabling malignant transformation and tumor progression, defects in apoptosis can result in resistance to cytotoxic cancer therapies. Much progress has been made in the delineation of the molecular pathways leading to apoptosis. This allows the identification of target molecules and lead compounds to develop novel therapies, which make use of this intrinsic death program for the treatment of cancer. Here, we review the current understanding of apoptotic signal transduction pathways, and strategies of their ther…

Segmentation, involvement and the reach-engagementrelationship: evidence from a QR code advertising campaign

2013

This paper presents a procedure that practitioners must follow before assessing the reach-­‐engagement relationship in a “pull” campaign. It is suggested to check for the independence between this relationship and that between segmentation and product involvement. If the two relationships are independent, then segmentation becomes less relevant when assessing the reach-­‐engagement relationship. Otherwise, an unobservable segmentation variable must be accounted for in the reach-­‐engagement relationship. These aspects of segmentation are never mentioned in the extant literature, which treats segmentation in “pull” campaigns the same way in which targeting is designed in “push” campaigns. Th…

GALACTOSE-FUNCTIONALISED POLYMERIC MICELLES AS HEPATOCYTE-TARGETED CARRIERS

2012

AGuIX modifications for active tumor targeting and radiolabelling

2014

International audience

Targeting of biotinylated compounds to its target tissue using a low-density lipoprotein receptor–avidin fusion protein

2003

The very high binding affinity of avidin to biotin is one of the highest to occur in nature. We constructed a fusion protein composed of avidin and the endocytotic LDL receptor in order to target biotinylated molecules to cells of the desired tissues. In addition to the native avidin, charge-mutated and nonglycosylated avidins were utilized as part of the fusion proteins, in order to modify its properties. All of the fusion protein versions retained the biotin-binding capacity. Although the specificity was not increased, however, fusion proteins composed of natural avidin and nonglycosylated avidin bound most efficiently to the biotinylated ligands. Fluorescence microscopy and atomic force …

Disruption of the retinitis pigmentosa 28 gene Fam161a in mice affects photoreceptor ciliary structure and leads to progressive retinal degeneration.

2014

Mutations in the FAM161A gene were previously identified as the cause for autosomal-recessive retinitis pigmentosa 28. To study the effects of Fam161a dysfunction in vivo, we generated gene-trapped Fam161a(GT/GT) mice with a disruption of its C-terminal domain essential for protein-protein interactions. We confirmed the absence of the full-length Fam161a protein in the retina of Fam161a(GT/GT) mice using western blots and showed weak expression of a truncated Fam161a protein by immunohistochemistry. Histological analyses demonstrated that photoreceptor segments were disorganized in young Fam161a(GT/GT) mice and that the outer retina was completely lost at 6 months of age. Reactive microglia…

Rapid, reproducible transduction of select forebrain regions by targeted recombinant virus injection into the neonatal mouse brain

2009

Viral vectors can mediate long-term gene expression in different regions of the brain. Recombinant adeno-associated virus (rAAV) and Lenti virus (LV) have both gained prominence due to their ability to achieve specific transduction of various neuronal populations. Whilst widespread gene delivery has been obtained by targeted injection of rAAV in various brain structures, LV has also been utilized for infection of stem cell populations for cell lineage tracing. Both viral vector systems are most commonly used for gene delivery in mature brains, but the great potential of somatic gene delivery into the neonate brain has not been systematically exploited. Here we provide a systematic guideline…