Curcumin has been reported as a radiosensitizer in prostate cancer. But the underlying mechanism is not well understood. In this study, we firstly assessed how curcumin affects the expression of miR-143/miR-145 cluster. Then, we investigated whether miR-143 is involved in regulation of radiosensitivity and its association with autophagy in prostate cancer cells. Our data showed that PC3, DU145 and LNCaP cells treated with curcumin had significantly restored miR-143 and miR-145 expression. Curcumin showed similar effect as 5-AZA-dC on reducing methylation of CpG dinucleotides in miR-143 promoter. In addition, curcumin treatment reduced the expression of DNMT1 and DNMT3B, which contribute to promoter hypermethylation of the miR-143/miR-145 cluster. Therefore, we infer that curcumin can restore miR-143 and miR-145 expression via hypomethylation. MiR-143 overexpression and curcumin pretreatment enhanced radiation induced cancer cell growth inhibition and apoptosis. MiR-143 and curcumin remarkably reduced radiation-induced autophagy in PC3 and DU145 cells. MiR-143 overexpression alone also reduced the basal level of autophagy in DU145 cells. Mechanistically, miR-143 can suppress autophagy in prostate cancer cells at least via downregulating ATG2B. Based on these findings, we infer that curcumin sensitizes prostate cancer cells to radiation partly via epigenetic activation of miR-143 and miR-143 mediated autophagy inhibition.
ALK-rearranged RCC is a rare subtype of adult RCC and is associated with distinct histological features and a poor prognosis. Identification of ALK-rearranged RCC has important clinical significance, because patients might benefit from ALK inhibitor therapy as used in lung adenocarcinoma.
A novel and regioselective approach to carbonyl-containing alkyl chlorides via silver-catalyzed ring-opening chlorination of cycloalkanols is reported. Concurrent C(sp(3))-C(sp(3)) bond cleavage and C(sp(3))-Cl bond formation efficiently occur with good yields under mild conditions, and the chlorinated products are readily transformed into other useful synthetic intermediates and drugs. The reaction features complete regioselectivity, high efficiency, and excellent practicality.
A video-on-demand (VOD) server needs to store hundreds of movie titles and to support thousands of concurrent accesses. This, technically and economically, imposes a great challenge on the design of the disk storage subsystem of a VOD server. Due to different demands for different movie titles, the numbers of concurrent accesses to each movie can differ a lot. We define access profile as the number of concurrent accesses to each movie title that should be supported by a VOD server. The access profile is derived based on the popularity of each movie title and thus serves as a major design goal for the disk storage subsystem. Since some popular (hot) movie titles may be concurrently accessed by hundreds of users and a current high-end magnetic disk array (disk) can only support tens of concurrent accesses, it is necessary to replicate and/or stripe the hot movie files over multiple disk arrays. The consequence of replication and striping of hot movie titles is the potential increase on the required number of disk arrays. Therefore, how to replicate, stripe, and place the movie files over a minimum number of magnetic disk arrays such that a given access profile can be supported is an important problem. In this paper, we formulate the problem of the video file allocation over disk arrays, demonstrate that it is a NP-hard problem, and present some heuristic algorithms to find the near-optimal solutions. The result of this study can be applied to the design of the storage subsystem of a VOD server to economically minimize the cost or to maximize the utilization of disk arrays.
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