| Target Validation Information | |||||
|---|---|---|---|---|---|
| Target ID | T95899 | ||||
| Target Name | mRNA of Clusterin | ||||
| Target Type | Clinical Trial |
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| Action against Disease Model | OGX-011 | A h uMan bladder cancer cell line, uM-UC-3, was continuously exposed to increasing doses of gemcitabine in vitro, and a gemcitabine-resistant cell line uM-UC-3R was developed. The role of sCLU-2 in chemoresistant phenotype acquired in both in vitro and in vivo was then analysed using antisense oligonucleotide targeting the sCLU-2 gene (OGX-011). Treatment of uM-UC-3R cells with OGX-011 resulted in a dose-dependent and sequence- specific inhibition in sCLU-2 expression. Furthermore, OGX-011 chemo-sensitized uM-UC-3R cells to gemcitabine in vitro with a reduction in the concentration that reduces the effect by 50% (IC50) from 100 nm to 10 nm. | [552884] | Drug Info | |
| The Effect of Target Knockout, Knockdown or Genetic Variations | Using clusterin-deficient (Clu-/-) mice, we investigated the role of clusterin after permanent middle cerebral artery occlusion (MCAO). In wild-type (WT) mice, clusterin mRNA displayed a sustained increase in the peri-infarct area from 14 to 30 days post-MCAO. Clusterin transcript was still present up to 90 days post-ischemia in astrocytes surrounding the core infarct. Western blot analysis also revealed an increase of clusterin in the ischemic hemisphere of WT mice, which culminates up to 30 days post-MCAO. Concomitantly, a worse structural restoration and higher n uMber of GFAP-reactive astrocytes in the vicinity of the infarct scar were observed in Clu-/- as compared to WT mice. These findings go beyond previous data supporting a neuroprotective role of clusterin in early ischemic events in that they demonstrate that this glycoprotein plays a central role in the remodeling of ischemic damage | [552884] | |||
| References | |||||
| Ref 552884 | Chemosensitization of gemcitabine-resistant human bladder cancer cell line both in vitro and in vivo using antisense oligonucleotide targeting the anti-apoptotic gene, clusterin. BJU Int. 2009 Feb;103(3):384-90. doi: 10.1111/j.1464-410X.2008.08098.x. Epub 2008 Oct 24. | ||||
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