ABSTRACTa db_289 539..546In rodents, a conditioned place preference (CPP) can be induced by morphine. In the current study, we designed a biased place conditioning paradigm to test the rewarding effects of morphine in freely moving rhesus monkeys. Five monkeys were first placed in three serial rooms with the doors open between them for three days. After this habituation period, during which baseline preference for each of the two end rooms was measured, CPP conditioning occurred when the monkeys were injected intramuscularly with morphine at an increasing dose (1.5, 3, 4.5 mg/kg) before they entered the non-preferred room and on alternate days, with saline before they entered the preferred room. Morphine and saline treatment lasted for six days, respectively. CPP was tested 24 hours after the end of CPP training. The result showed that in all five monkeys, CPP was induced by the morphine treatment. The preference lasted for at least 15.3 Ϯ 1.7 months.
microRNAs are small non-coding RNAs that regulate gene expression post-transcriptionally. The mRNA targets of microRNAs are usually determined based on complementarily to the 5′ end of the microRNA; the area termed the seed sequence. One microRNA can have more than 100 mRNA targets that are usually inhibited by ∼50%. The expression of microRNAs has been shown to be dysregulated in numerous cancer types. These dysregulated microRNAs can act to either positively or negatively regulate initiation, proliferation and metastasis of cancer cells. Some of the most important pathways in cancer biology (e.g. the Ras and p53 pathways) have been shown to interact with microRNAs. Therefore, both inhibiting and replacing microRNAs have therapeutic potential in oncology. We are using technology similar to that used for antisense oligonucleotides and lipid nanoparticle formulated siRNAs, both of which are currently in clinical trials for cancer, to determine the best potential microRNA based therapeutics to develop as drugs. In this report we will focus on our attempts to introduce mimics of microRNAs known to be down-regulated in tumors (e.g. miR-34a). Initial experiments were performed in wild-type mice and demonstrated the ability to deliver microRNA mimics to the liver and to affect gene expression in a seed sequence-dependent manner. These results, along with effects of successful microRNA introduction into an orthotopic xenograft model of hepatocellular carcinoma will be presented. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4044.
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