Increased expression of the sodium iodide symporter (NIS) is required for effective radioiodine treatment and reporter gene imaging of breast cancer. We investigated the effect of retinoic acid on adenovirus-mediated expression of the human NIS gene in the MCF-7 breast cancer cell line. METHODS: The MCF-7 cell line was infected with recombinant adenovirus carrying the human NIS gene (Rad-NIS). Levels of NIS messenger RNA (mRNA) and protein expression and radioiodine ((125)I) uptake were measured to evaluate adenovirus-mediated NIS gene expression in wild-type and Rad-NIS-infected MCF-7 cells after treatment with all-trans-retinoic acid (ATRA; 10(-8)-10(-6) mol/L). RESULTS: The transduction efficiency of adenovirus in MCF-7 cells at a multiplicity of infection (MOI) of 50 was >60%. After incubation with 10(-6) mol/L ATRA, the mRNA level in Rad-NIS-infected MCF-7 cells increased to 118.5 times that of wild-type MCF-7 cells, whereas the mRNA level in wild-type MCF-7 cells showed only a 2.1-fold increase. Western blot, immunocytochemical staining, and flow cytometry analyses showed that NIS protein expression in MCF-7 cells infected with Rad-NIS increased after ATRA treatment. With ATRA treatment, the amount of (125)I uptake increased in a dose-dependent manner (P < 0.001). The (125)I uptake in wild-type MCF-7 cells increased 3.1-, 5.5-, and 7.6-fold with treatment with 10(-8), 10(-7), and 10(-6) mol/L ATRA, respectively. Rad-NIS-infected cells showed a 4.0-fold increase in (125)I uptake. Treatment of Rad-NIS-infected cells with 10(-8), 10(-7), and 10(-6) mol/L ATRA increased (125)I uptake by 4.9-, 8.2-, and 27.6-fold, respectively, compared with wild-type MCF-7 cells. The level of NIS expression in Rad-NIS-infected MCF-7 cells treated with 10(-6) mol/L ATRA (245.0 +/- 13.7 pmol/10(6) cells) was much greater than the sum of the expression levels seen in ATRA-treated wild-type cells and Rad-NIS-infected wild-type cells. CONCLUSION: Retinoic acid increases adenovirus-mediated NIS expression in MCF-7 cells. Our results indicate that improved efficiency of NIS gene therapy or reporter imaging in breast cancer may be possible with retinoic acid treatment. 相似文献
We developed a technique of translocation of the pulmonary artery anterior to the ascending aorta without transection of the aorta in the repair of tetralogy of Fallot with absent pulmonary valve. Our technique includes detachment of the main pulmonary artery (MPA) from the pulmonary annulus, vertical division of the MPA, anterior translocation of the pulmonary artery with patch augmentation between the vertically divided MPA. 相似文献
Background: Morphine pretreatment via activation of [delta]1-opioid receptors induces cardioprotection. In this study, the authors determined whether morphine preconditioning induces ischemic tolerance in neurons.
Methods: Cerebellar brain slices from adult Sprague-Dawley rats were incubated with morphine at 0.1-10 [mu]m in the presence or absence of various antagonists for 30 min. They were then kept in morphine- and antagonist-free buffer for 30 min before they were subjected to simulated ischemia (oxygen-glucose deprivation) for 20 min. After being recovered in oxygenated artificial cerebrospinal fluid for 5 h, they were fixed for morphologic examination to determine the percentage of undamaged Purkinje cells.
Results: The survival rate of Purkinje cells was significantly higher in slices preconditioned with morphine (>= 0.3 [mu]m) before the oxygen-glucose deprivation (57 +/- 4% at 0.3 [mu]m morphine) than that of the oxygen-glucose deprivation alone (39 +/- 3%, P < 0.05). This morphine preconditioning-induced neuroprotection was abolished by naloxone, a non-type-selective opioid receptor antagonist, by naltrindole, a selective [delta]-opioid receptor antagonist, or by 7-benzylidenenaltrexone, a selective [delta]1-opioid receptor antagonist. However, the effects were not blocked by the [mu]-, [kappa]-, or [delta]2-opioid receptor antagonists, [beta]-funaltrexamine, nor-binaltorphimine, or naltriben, respectively. Morphine preconditioning-induced neuroprotection was partially blocked by the selective mitochondrial adenosine triphosphate-sensitive potassium channel antagonist, 5-hydroxydecanoate, or the mitochondrial electron transport inhibitor, myxothiazol. None of the inhibitors used in this study alone affected the simulated ischemia-induced neuronal death. 相似文献