Search results for "RNA interference"
showing 10 items of 202 documents
Open-label extension study of the RNAi therapeutic ALN-VSP02 in cancer patients responding to therapy.
2012
3062 Background: ALN-VSP02 is an RNA interference (RNAi) therapeutic comprised of lipid nanoparticle-formulated small interfering RNAs targeting vascular endothelial growth factor (VEGF)-A and kinesin spindle protein (KSP). In a phase 1 trial, ALN-VSP02 administered as an iv infusion q2 wks was well-tolerated and showed evidence of anti-VEGF pharmacology and antitumor activity. Methods: Patients treated on the phase I trial with stable disease (SD) or better after 4 months (8 doses) were eligible to continue on an extension study until disease progression. Main objectives included continued evaluation of safety/tolerability and assessment of disease response. Results: Seven of 37 patients …
Tracheal development and the von Hippel-Lindau tumor suppressor homolog in Drosophila.
2000
von Hippel-Lindau disease is a hereditary cancer syndrome. Mutations in the VHL tumor suppressor gene predispose individuals to highly vascularized tumors. However, VHL-deficient mice die in utero due to a lack of vascularization in the placenta. To resolve the contradiction, we cloned the Drosophila VHL homologue (d-VHL) and studied its function. It showed an overall 50% similarity to the human counterpart and 76% similarity in the crucial functional domain: the elongin C binding site. The putative d-VHL protein can bind Drosophila elongin C in vitro. During embryogenesis, d-VHL is expressed in the developing tracheal regions where tube outgrowth no longer occurs. Reduced d-VHL activity (u…
GADD45α is highly expressed in pancreatic ductal adenocarcinoma cells and required for tumor cell viability
2005
Pancreatic ductal adenocarcinoma is one of the most common causes of cancer death in the western civilization. Recently, NF-kappaB has been shown to be activated in pancreatic ductal adenocarcinoma through constitutive activation of IkappaB kinase (IKK). Inhibition of NF-kappaB by a super-inhibitor of NF-kappaB--delta-N-IkappaBalpha--resulted in impaired proliferation and induction of apoptosis, suggesting an important role of NF-kappaB in pancreatic tumorigenesis. Downstream target genes of IkappaBalpha have not been elucidated in pancreatic ductal adenocarcinoma in detail. Using expression profiling by cDNA array analysis of pancreatic ductal adenocarcinoma cell lines stably transfected w…
Small interfering RNA (siRNA) inhibits the expression of the Her2/neu gene, upregulates HLA class I and induces apoptosis of Her2/neu positive tumor …
2003
Silencing of a specific mRNA using double stranded RNA oligonucleotides represents one of the newest technologies for suppressing a specific gene product. Small interfering RNA (siRNA) are 21 nucleotides long, double stranded RNA fragments that are identical in sequence to the target mRNA. We designed 3 such siRNA against the Her2/neu (HER2) gene. The HER2 gene is known to play an important role in the oncogenesis of several types of cancers, such as breast, ovarian, colon and gastric cancers. Introduction of the siRNA into HER2 positive tumor lines in vitro greatly reduced the cell surface expression of the HER2 protein. Concurrently, a range of effects on cell physiology, such as growth i…
Analysis of Possible Mechanisms Accounting for Raf-1 Kinase Inhibitor Protein Downregulation in Hepatocellular Carcinoma
2012
Abstract Raf-1 kinase inhibitor protein (RKIP) is a tumor and metastasis suppressor that promotes drug-induced apoptosis in cancer cells. It is frequently downregulated, both at the mRNA and protein level, in hepatocellular carcinoma (HCC), but the mechanisms leading to this reduction are obscure. We sequenced the whole RKIP gene in three human HCC cell lines (HA22T/VGH, HepG2, and Hep3B), and in five clinical HCC samples, but could not find any gene variant that might account for their low RKIP levels. We also examined whether gene methylation may be responsible for the altered RKIP expression. No methylation of the RKIP gene was found in the tumor samples, while among the cell lines only …
miR-133a Enhances the Protective Capacity of Cardiac Progenitors Cells after Myocardial Infarction
2014
Summary miR-133a and miR-1 are known as muscle-specific microRNAs that are involved in cardiac development and pathophysiology. We have shown that both miR-1 and miR-133a are early and progressively upregulated during in vitro cardiac differentiation of adult cardiac progenitor cells (CPCs), but only miR-133a expression was enhanced under in vitro oxidative stress. miR-1 was demonstrated to favor differentiation of CPCs, whereas miR-133a overexpression protected CPCs against cell death, targeting, among others, the proapoptotic genes Bim and Bmf. miR-133a-CPCs clearly improved cardiac function in a rat myocardial infarction model by reducing fibrosis and hypertrophy and increasing vasculari…
Inducing Cold-Sensitivity in the Frigophilic Fly Drosophila montana by RNAi.
2016
Cold acclimation is a critical physiological adaptation for coping with seasonal cold. By increasing their cold tolerance individuals can remain active for longer at the onset of winter and can recover more quickly from a cold shock. In insects, despite many physiological studies, little is known about the genetic basis of cold acclimation. Recently, transcriptomic analyses in Drosophila virilis and D. montana revealed candidate genes for cold acclimation by identifying genes upregulated during exposure to cold. Here, we test the role of myo-inositol-1-phosphate synthase (Inos), in cold tolerance in D. montana using an RNAi approach. D. montana has a circumpolar distribution and overwinters…
Identification and characterisation of the dopamine receptor II from the cat flea Ctenocephalides felis (CfDopRII)
2006
International audience; G protein-coupled receptors (GPCRs) represent a protein family with a wide range of functions. Approximately 30% of human drug targets are GPCRs, illustrating their pharmaceutical relevance. In contrast, the knowledge about invertebrate GPCRs is limited and is mainly restricted to model organisms like Drosophila melanogaster and Caenorhabditis elegans. Especially in ectoparasites like ticks and fleas, only few GPCRs are characterised. From the cat flea Ctenocephalides felis, a relevant parasite of cats and dogs, no GPCRs are known so far. Thus, we performed a bioinformatic analysis of available insect GPCR sequences from the honeybee Apis mellifera, the mosquito Anop…
Live cell imaging of duplex siRNA intracellular trafficking.
2015
Intracellular distribution of siRNA after in vitro transfection typically depends on lipopolyplexes, which must release the siRNA into the cytosol. Here, the fate of siRNAs was monitored by FRET-based live cell imaging. Subsequent to in situ observation of uptake and release processes, this approach allowed the observation of a number of hitherto uncharacterized intracellular distribution and degradation processes, commencing with a burst of endosomal releases, followed, in some cases, by fast siRNA influx into the nucleus. The continued observation of intact siRNA against a background of free fluorophores resulting from advanced degradation was possible by a specifically developed imaging …
Endothelial transcriptomic changes induced by oxidized low density lipoprotein disclose an up-regulation of Jak-Stat pathway.
2015
Oxidized low density lipoproteins (oxLDLs) act as an etiological factor in the development of atherosclerosis by modifying the biological properties of endothelial cells through mechanisms of vascular inflammation. To deepen the oxLDL changes at cellular level, a transcriptomic analysis of human umbilical artery endothelial cells (HUAECs) treated with oxLDL was performed to identify the modified signaling pathways. Total RNA was isolated from HUAECs treated with oxLDL (100 μg/ml). Gene expression analysis was carried out using Affymetrix oligonucleotide microarrays. Biological pathway analysis was performed using Ingenuity Pathway Analysis software. Microarray assay demonstrated that oxLDL …