Search

This paper concerns the stationary subsonic or sonic–subsonic solution of the electric potential driven problem to the isentropic hydrodynamic model for semiconductors. We give a necessary and sufficient condition to ensure the existence of this kind of solution. Specifically, there exists a subsonic or sonic–subsonic solution to this problem if and only if 0 ≤ ϕ r ≤ ϕ ̄ , with the number ϕ ̄ = O 1 τ . Here, ϕ r is the right side electric potential and τ is the relaxation time. Moreover, there is a number ϕ ̃ ∈ (0 , ϕ ̄ ] such that when ϕ r = ϕ ̃ , there exists a sonic–subsonic solution. In this way, we show the influence of the relationship between the boundary value of the electric potential and the semiconductor effect on the existence of this kind of solution. Finally, we prove the uniqueness of subsonic solution by the energy method under the assumption that ϕ r and ϕ r τ are both small enough. [ABSTRACT FROM AUTHOR]

Summary The BH4 domain of Bcl2 is required for its antiapoptotic function, thus constituting a promising anticancer target. We identified a small-molecule Bcl2-BH4 domain antagonist, BDA-366, that binds BH4 with high affinity and selectivity. BDA-366-Bcl2 binding induces conformational change in Bcl2 that abrogates its antiapoptotic function, converting it from a survival molecule to a cell death inducer. BDA-366 suppresses growth of lung cancer xenografts derived from cell lines and patient without significant normal tissue toxicity at effective doses. mTOR inhibition upregulates Bcl2 in lung cancer cells and tumor tissues from clinical trial patients. Combined BDA-366 and RAD001 treatment exhibits strong synergy against lung cancer in vivo. Development of this Bcl2-BH4 antagonist may provide a strategy to improve lung cancer outcome. [ABSTRACT FROM AUTHOR]

Summary Platinum-based chemotherapeutics represent a mainstay of cancer therapy, but resistance limits their curative potential. Through a kinome RNAi screen, we identified microtubule-associated serine/threonine kinase 1 (MAST1) as a main driver of cisplatin resistance in human cancers. Mechanistically, cisplatin but no other DNA-damaging agents inhibit the MAPK pathway by dissociating cRaf from MEK1, while MAST1 replaces cRaf to reactivate the MAPK pathway in a cRaf-independent manner. We show clinical evidence that expression of MAST1, both initial and cisplatin-induced, contributes to platinum resistance and worse clinical outcome. Targeting MAST1 with lestaurtinib, a recently identified MAST1 inhibitor, restores cisplatin sensitivity, leading to the synergistic attenuation of cancer cell proliferation and tumor growth in human cancer cells and patient-derived xenograft models. [ABSTRACT FROM AUTHOR]