HIF-α Effects on c-Myc Distinguish Two Subtypes of Sporadic VHL-Deficient Clear Cell Renal Carcinoma

VHL tumor suppressor loss results in hypoxia inducible factor-alpha (HIF-α) stabilization, and occurs in 70% of sporadic clear cell renal carcinomas (ccRCCs). To determine whether opposing influences of HIF-1α and HIF-2α on c-Myc activity regulate human ccRCC progression, we analyzed VHL genotype and HIF-α expression in 160 primary tumors, which segregated into three groups with distinct molecular characteristics. Interestingly, ccRCCs with intact VHL, as well as pVHL-deficient, HIF-1α/HIF-2α expressing ccRCCs, exhibited enhanced Akt/mTOR and ERK/MAPK signaling. In contrast, pVHL-deficient ccRCCs expressing only HIF-2α displayed elevated c-Myc activity, resulting in enhanced proliferation and resistance to replication stress. These reproducible distinctions in ccRCC behavior delineate HIF-α effects on c-Myc in vivo and suggest molecular criteria for selecting targeted therapies

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Efficient Clustering for Multicast Key Distribution in MANETs

http://www.springer.com/Securing multicast communications in ad hoc networks must consider several challenging factors such as high nodes mobility, limited bandwidth and constrained energy. Moreover, the establishment of a key management protocol within ad hoc environment meets the "1 affects n" problem, which is more critical in such type of networks, due to the high dynamicity of groups. In this papers, we present an efficient clustering scheme for multicast key distribution in Mobile ad hoc networks. This scheme divides the multicast group into clusters, according to the localization of the group members and their mobility. Simulations indicate a valuable reduction in the average latency of keys distribution and a promising reduction in energy consumption. Analysis also shows that our scheme is scalable