Search results for " Small"

Epigenetic siRNA and Chemical Screens Identify SETD8 Inhibition as a Therapeutic Strategy for p53 Activation in High-Risk Neuroblastoma

2017

Given the paucity of druggable mutations in high-risk neuroblastoma (NB), we undertook chromatin-focused small interfering RNA and chemical screens to uncover epigenetic regulators critical for the differentiation block in high-risk NB. High-content Opera imaging identified 53 genes whose loss of expression led to a decrease in NB cell proliferation and 16 also induced differentiation. From these, the secondary chemical screen identified SETD8, the H4K20me1 methyltransferase, as a druggable NB target. Functional studies revealed that SETD8 ablation rescued the pro-apoptotic and cell-cycle arrest functions of p53 by decreasing p53K382me1, leading to activation of the p53 canonical pathway. I…

Apollon gene silencing induces apoptosis in breast cancer cells via p53 stabilisation and caspase-3 activation

2009

We analysed the effects of small interfering RNA (siRNA)-mediated silencing of Apollon, a member of the inhibitors of apoptosis protein family, on the proliferative potential and ability of human breast cancer cell lines to undergo apoptosis. In wild-type p53 ZR75.1 cells, Apollon knockdown resulted in a marked, time-dependent decline of cell growth and an increased rate of apoptosis, which was associated with p53 stabilisation and activation of the mitochondrial-dependent apoptotic pathway. Pre-incubation of cells with a p53-specific siRNA resulted in a partial rescue of cell growth inhibition, as well as in a marked reduction of the apoptotic response, indicating p53 as a major player in …

Induction of body weight loss through RNAi-knockdown of APOBEC1 gene expression in transgenic rabbits

2014

In the search of new strategies to fight against obesity, we targeted a gene pathway involved in energy uptake. We have thus investigated the APOB mRNA editing protein (APOBEC1) gene pathway that is involved in fat absorption in the intestine. The APOB gene encodes two proteins, APOB100 and APOB48, via the editing of a single nucleotide in the APOB mRNA by the APOBEC1 enzyme. The APOB48 protein is mandatory for the synthesis of chylomicrons by intestinal cells to transport dietary lipids and cholesterol. We produced transgenic rabbits expressing permanently and ubiquitously a small hairpin RNA targeting the rabbit APOBEC1 mRNA. These rabbits exhibited a moderately but significantly reduced …

La prise en compte de la durabilité dans les stratégies marketing des PME : apports et limites

2011

Nous examinons dans cet article comment des directeurs de PME agroalimentaires à fort ancrage territorial s’approprient la notion de développement durable et l’expriment dans leurs stratégies marketing. Nous examinons successivement leur vision du lien entre développement durable et performance, l’impact des caractéristiques environnementales sur leurs pratiques et les limites qu’ils perçoivent à cette volonté d’intégrer la durabilité dans leur stratégie au moment de sa mise en œuvre. Au-delà de l’argument commercial, la durabilité apparaît comme un levier intéressant du projet d’entreprise et de la mobilisation des salariés. Néanmoins, la démarche comporte aussi des limites.

Improvements in Rational Design Strategies of Inulin Derivative Polycation for siRNA Delivery.

2016

The advances of short interfering RNA (siRNA)-mediated therapy provide a powerful option for the treatment of many diseases, including cancer, by silencing the expression of targeted genes involved in the progression of the pathology. On this regard, a new pH-responsive polycation derived from inulin, Inulin-g-imidazole-g-diethylenetriamine (INU-IMI-DETA), was designed and employed to produce INU-IMI-DETA/siRNA "Inulin COmplex Nanoaggregates" (ICONs). The experimental results showed that INU-IMI-DETA exhibited strong cationic characteristics and high solubility in the pH range 3-5 and self-aggregation triggered by pH increase and physiological salt concentration. INU-IMI-DETA showed as well…

Increased plasma resistin concentrations are associated with atherogenic small, dense low-density lipoproteins in patients with type-2 diabetes

2010

Quantificazione del merito creditizio e costo del denaro per le imprese italiane: caratteristiche e simulazioni spaziali in Italia

2012

L’economia dei flussi di cassa è il Leitmotiv di questi anni, e il denaro condiziona i comportamenti individuali e collettivi. Economie tradizionalmente solide entrano in crisi se non riscuotono la fiducia dei mercati, e le famiglie, come le imprese, difficilmente riescono a programmare il proprio futuro senza le risorse finanziarie occorrenti per le proprie attività. Nel complesso periodo che stiamo vivendo, è opinione diffusa che l’uscita dalla crisi economica derivi da cambiamenti epocali nell’organizzazione dei sistemi produttivi e finanziari nonché negli stili di vita, rivisitando il significato stesso di sviluppo economico. In tale contesto la marginalità finanziaria, intesa come vant…

Polymeric nanoparticles for siRNA delivery: Production and applications

2017

Gene therapy through the use of siRNA and a polymeric carrier are becoming an efficient therapeutic option to conventional pharmaceutical formulations for the treatment of deadly diseases, such as cancer, pulmonary, ocular and neurodegenerative diseases. However, several considerations regarding the stability, formulation, and efficacy have to be faced up until these systems could be considered to be a marketable pharmaceutical products for to extend siRNA application to clinical practice. This review is focused on the key challenges of siRNA therapeutics, with special attention on the faced obstacles and on the formulation-related difficulties, providing a list of requirements needed for o…

Development of New Targeted Inulin Complex Nanoaggregates for siRNA Delivery in Antitumor Therapy.

2021

Here, a novel strategy of formulating efficient polymeric carriers based on the already described INU-IMI-DETA for gene material whose structural, functional, and biological properties can be modulated and improved was successfully investigated. In particular, two novel derivatives of INU-IMI-DETA graft copolymer were synthesized by chemical functionalisation with epidermal growth factor (EGF) or polyethylenglycol (PEG), named INU-IMI-DETA-EGF and INU-IMI-DETA-PEG, respectively, in order to improve the performance of already described “inulin complex nanoaggregates” (ICONs). The latter were thus prepared by appropriately mixing the two copolymers, by varying each component from 0 to 100 wt%…

A fluorescence study of the loading and time stability of doxorubicin in sodium cholate/PEO-PPO-PEO triblock copolymer mixed micelles

2019

Abstract Hypothesis Doxorubicin hydrochloride (DX) is one of the most powerful anticancer agents though its clinical use is impaired by severe undesired side effects. DX encapsulation in nanocarrier systems has been introduced as a mean to reduce its toxicity. Micelles of the nonionic triblock copolymers of poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO) (PEO-PPO-PEO), are very promising carrier systems. The positive charge of DX confines the drug to the hydrophilic corona region of the micelles. The use of mixed micelles of PEO-PPO-PEO copolymers and a negatively charged bile salt should favour the solubilization of DX in the apolar core region of the micelles. Experiments We st…