The potassium channel Kv1.3 is highly expressed in the mitochondria of various cancerous cells. Here we show that direct inhibition of Kv1.3 using two mitochondria-targeted inhibitors alters mitochondrial function and leads to reactive oxygen species (ROS)-mediated death of even chemoresistant cells independently of p53 status. These inhibitors killed 98% of ex vivo primary chronic B-lymphocytic leukemia tumor cells while sparing healthy B cells. In orthotopic mouse models of melanoma and pancreatic ductal adenocarcinoma, the compounds reduced tumor size by more than 90% and 60%, respectively, while sparing immune and cardiac functions. Our work provides direct evidence that specific pharmacological targeting of a mitochondrial potassium channel can lead to ROS-mediated selective apoptosis of cancer cells in vivo, without causing significant side effects.

The application of polymer “brushes”, with their unique physicochemical properties, has led to a radical change in the way we functionalize biomaterials or formulate hybrids; however, their attractive traits can be largely surpassed by applying different polymer topologies, beyond the simple linear chain. Cyclic and loop brushes provide enhanced steric stabilization, improved biopassivity, and lubrication compared to their linear analogues. Focusing on poly­(2-ethyl-2-oxazoline) (PEOXA), an emerging polymer in nanobiotechnology, we systematically investigate how topology effects determine the structure of PEOXA brushes and to what extent technologically relevant properties such as protein resistance, nanomechanics, and nanotribology can be tuned by varying brush topology. The highly compact structure of cyclic PEOXA brushes confers an augmented entropic barrier to the surface, efficiently hindering unspecific interactions with biomolecules. Moreover, the intrinsic absence of chain ends at the cyclic-brush interface prevents interdigitation when two identical polymer layers are sheared against each other, dramatically reducing friction. Loop PEOXA brushes present structural and interfacial characteristics that are intermediate between those of linear and cyclic brushes, which can be precisely tuned by varying the relative concentration of loops and tails within the assembly. Such topological control allows biopassivity to be progressively increased and friction to be tuned.

Non-equilibrium plasma based technologies are currently being developed for the abatement of volatile organic compounds (VOCs). The promising results obtained so far encourage efforts in fundamental research to improve our knowledge of the processes involved. To gain insight into the role played by analyte-derived ionic species we have investigated the ion chemistry of trichloroethylene (TCE), a representative VOC, in air at ambient pressure by means of an atmospheric pressure chemical ionization commercial mass spectrometer. Different experimental conditions were examined with regard to the following parameters: ion source temperature, water and TCE concentrations, and extraction potential. Notably, modulation of the variable extraction potential provided a means to probe structure and reactivity of the ionic species of interest. Products resulting from TCE oxidation were observed in the analysis of both positive and negative ions. Particularly prominent is a C 2 H 2 Cl 2 O + . species, likely of enol structure, due to reaction with water. A reaction scheme is proposed based on nucleophilic addition of water to ionized TCE followed by elimination of HCl. The negative ion chemistry of TCE is dominated by Cl -and its clusters with water and TCE. At low temperature and with water in high concentration very large positive and negative ion hydrate clusters (with up to 50 water molecules) could be observed. © 1997 by John Wiley & Sons, Ltd. Received 8 July 1997; Revised 2 September 1997; Accepted 8 September 1997 Rapid. Commun. Mass Spectrom. 11, 1687-1694 (1997 Control of volatile organic compounds (VOCs) in the atmosphere is a major environmental problem due to their great proliferation and to limitations of the traditional methods of abatement (incineration, catalytic oxidation and carbon adsorption).1 Among the alternative approaches being presently developed, nonequilibrium plasma-based technologies, using either high energy electron beams or electrical discharges including corona discharges, appear particularly promising. [2][3][4] Since most of the electrical energy used for producing a non-equilibrium plasma ends up in energetic electrons rather than gas heating, this approach is particularly suited for the cost-effective treatment of large volumes of gaseous effluents containing low concentrations of VOC produced by many different manufacturing industries in which volatile organic solvents are used. The products observed under most conditions include CO, CO 2 , and, for chlorinated VOCs, HCl and Cl 2 . In some cases additional products have been detected corresponding to some intermediate stages of oxidation, such as phosgene, 1,1-dichloroethene and chloroacetylchloride from 1,1,1-trichloroethane 5 and phosgene and dichloroacetylchloride from trichloroethylene (TCE). 6 In recent publications, kinetic analysis and mechanistic interpretations have also been presented for the decomposition of representative VOCs in non-equilibrium plasma. 3,5,7 It is generally accepted that the major decay routes involve radic...

AUC(Pt) was ∼2- to ∼25-fold higher in tissues than in blood; this may explain its bioactivity despite barely detectable blood levels. Of particular interest is the high fraction of nonmetabolized Pt in the brain, given the reports of its activity at the level of the central nervous system.

No abstract