In light of the potential use of the thiazolidinedione family of peroxisome proliferator-activated receptor-␥ (PPAR␥) agonists in prostate cancer treatment, this study assessed the mechanism by which these agents suppress prostate-specific antigen (PSA) secretion in prostate cancer cells. Two lines of evidence indicate that the effect of thiazolidinediones on PSA downregulation is independent of PPAR␥ activation. First, this thiazolidinedione-mediated PSA down-regulation is structure-specific irrespective of the relative PPAR␥ agonist potency. Second, the PPAR␥-inactive analogs of troglitazone and ciglitazone [⌬2TG (5-[4-(6-hydroxy-2,5,7,8-tetramethyl-chroman-2-yl-methoxy)-benzylidene]-thiazolidine-2,4-dione) and ⌬2CG (5-[4-(1-methyl-cyclohexylmethoxy)-benzylidene]-thiazolidine-2,4-dione), respectively] exhibit higher potency than the parent compound in inhibiting dihydrotestosterone (DHT)-stimulated PSA secretion. Although 10 M troglitazone and ⌬2TG significantly inhibit PSA secretion, they do not alter the expression level of androgen receptor (AR) or interfere with DHT-activated nuclear translocation of AR. However, reporter gene and chromatin immunoprecipitation studies indicate that troglitazone and ⌬2TG block AR recruitment to the androgen response elements within the PSA promoter. Thus, this study raises the question of whether the ability of oral troglitazone to reduce PSA levels in prostate cancer patients is therapeutically relevant. A major concern is that the concentration for troglitazone to mediate antitumor effects is severalfold higher than that of PSA down-regulation, which is difficult to attain at therapeutic doses. Nevertheless, it is noteworthy that troglitazone and ⌬2TG at high doses were able to inhibit AR expression. From a translational perspective, separation of PPAR␥ agonist activity from AR down-regulation provides a molecular basis to use troglitazone as a platform to design AR-ablative agents.
Background: During the SARS epidemic, healthcare utilization and medical services decreased significantly. However, the long-term impact of SARS on hospital performance needs to be further discussed.
In order to produce communication devices compliant with the LTE standard, a terminal manufacturer must perform a series of tests before mass production. This work analyzes the test cases and results of LTE Protocol Conformance Test (PCT) and Interoperability Test (IOT) for the user equipment (UE). We conduct 175 PCT test cases from the 3GPP specifications and the results show a PCT pass ratio of about 80%. IOT consists of 9 test cases selected by the manufacturers based on an agreed set of important test cases; only a few Devices under Test (DUTs) fail the IOT. Further analysis reveals that there exists a many-to-many mapping between PCT cases and IOT cases: a total of 42 PCT cases, i.e., 24% of PCT, map to all 9 IOT cases, and a PCT case might also map to several IOT cases. On average, every IOT case maps to 13 different PCT cases. The PCT cases that do not have mapped counterparts in IOT are mostly Layer 2 test cases. This is because most of the IOT test flows use Layer 3 parameters to determine passing or not without changing the default Layer 2 parameters. Passing IOT does not warrant passing PCT since PCT has requirements that are more rigid.
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