BACKGROUND: Here, we explore the therapeutic potential of dasatinib, a small-molecule inhibitor that targets multiple cytosolic and membrane-bound tyrosine kinases, including members of the Src kinase family, EphA2, and focal adhesion kinase for the treatment of ovarian cancer. METHODS: We examined the effects of dasatinib on proliferation, invasion, apoptosis, cell-cycle arrest, and kinase activity using a panel of 34 established human ovarian cancer cell lines. Molecular markers for response prediction were studied using gene expression profiling. Multiple drug effect/combination index (CI) isobologram analysis was used to study the interactions with chemotherapeutic drugs. RESULTS: Concentration-dependent anti-proliferative effects of dasatinib were seen in all ovarian cancer cell lines tested, but varied significantly between individual cell lines with up to a 3 log-fold difference in the IC 50 values (IC 50 range: 0.001 -11.3 mmol l À1 ). Dasatinib significantly inhibited invasion, and induced cell apoptosis, but less cell-cycle arrest. At a wide range of clinically achievable drug concentrations, additive and synergistic interactions were observed for dasatinib plus carboplatin (mean CI values, range: 0.73 -1.11) or paclitaxel (mean CI values, range: 0.76 -1.05). In this study, 24 out of 34 (71%) representative ovarian cancer cell lines were highly sensitive to dasatinib, compared with only 8 out of 39 (21%) representative breast cancer cell lines previously reported. Cell lines with high expression of Yes, Lyn, Eph2A, caveolin-1 and 2, moesin, annexin-1, and uPA were particularly sensitive to dasatinib. CONCLUSIONS: These data provide a clear biological rationale to test dasatinib as a single agent or in combination with chemotherapy in patients with ovarian cancer.

Knowledge of end-to-end path capacity is useful for video/audio stream adaptation, network management and overlay design. Capacity estimation in wired and last-hop wireless networks has been extensively investigated, but a thorough and systematic study in ad hoc, multihop wireless networks is still lacking. Yet the rate of a wireless link can change dynamically (and rapidly) due to changes in interference, distance or energy optimization policy.Timely knowledge of path capacity is key to efficient routing, traffic management and application deployment. In this paper, we present AdHoc Probe, a packet-pair based technique, to estimate end-to-end path capacity in ad hoc wireless networks. We apply AdHoc Probe to path capacity estimation in auto rate wireless networks with variable displacement and interference; and, in remote wireless networks across the Internet. Using analysis, simulation and testbed experiments, we show AdHoc Probe can withstand mobility and is able to trace the rate adaptation of wireless networks timely and correctly. AdHoc Probe is simpler, faster and much less intrusive than current schemes.

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Abstract. Real-time video streaming with rate adaptation to network load/congestion represents an efficient solution to its coexistence with conventional TCP data services. Naturally, the streaming rate control must be efficient, smooth and TCP friendly. As multimedia clients become mobile, these properties must be preserved also over wireless links. In particular, they must be robust to random wireless losses. Existing schemes such as TCP Friendly Rate Control (TFRC) perform well in the wired Internet, but show serious performance degradation in the presence of random wireless losses. In this paper we introduce the Video Transport Protocol (VTP) with a new rate control mechanism based on the Achieved Rate (AR) estimation and Loss Discrimination Algorithm. We show that VTP can preserve efficiency without causing additional performance degradation to TCP, in both error-free and error-prone situations.