Histone deacetylase (HDAC) inhibitors can induce various transformed cells to undergo growth arrest and/or death. Suberoylanilide hydroxamic acid (SAHA) is an HDAC inhibitor which is in phase I/II clinical trials and has shown antitumor activity in hematologic and solid tumors at doses well tolerated by patients. HDAC is the target for SAHA, but the mechanisms of the consequent induced death of transformed cells are not completely understood. In this study, we report that SAHA induced polyploidy in human colon cancer cell line HCT116 and human breast cancer cell lines, MCF-7, MDA-MB-231, and MBA-MD-468, but not in normal human embryonic fibroblast SW-38 and normal mouse embryonic fibroblasts. The polyploid cells lost the capacity for proliferation and committed to senescence. The induction of polyploidy was more marked in HCT116 p21 WAF1 À/À or HCT116 p53À/À cells than in wild-type HCT116. The development of senescence of SAHA-induced polyploidy cells was similar in all colon cell lines. The present findings indicate that the HDAC inhibitor could exert antitumor effects by inducing polyploidy, and this effect is more marked in transformed cells with nonfunctioning p21 WAF1 or p53 genes. (Cancer Res 2005; 65(17): 7832-9)
On demand routing protocols provide scalable and cost-effective solutions for packet routing in mobile wireless ad hoc networks. The paths generated by these protocols may deviate far from the optimal because of the lack of knowledge about the global topology and the mobility of nodes. Routing optimality affects network performance and energy consumption, especially when the load is high. In this paper, we define routing optimality using different metrics such as path length, energy consumption along the path, and energy aware load balancing among the nodes. We then propose a framework of Self-Healing and Optimizing Routing Techniques (SHORT) for mobile ad hoc networks. While using SHORT, all the neighboring nodes monitor the route and try to optimize it if and when a better local subpath is available. Thus SHORT enhances performance in terms of bandwidth and latency without incurring any significant additional cost. In addition, SHORT can be also used to determine paths that result in low energy consumption or to optimize the residual battery power. Thus, we have detailed two broad classes of SHORT algorithms: Path-Aware SHORT and Energy-Aware SHORT. Finally, we evaluate SHORT using the ns-2 simulator. The results demonstrate that the performance of existing routing schemes can be significantly improved using the proposed SHORT algorithms.
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