DNA-alkylating agents that are platinum complexes induce apoptotic responses and have wide application in cancer therapy. The potential for platinum compounds to modulate signal transduction events that contribute to their therapeutic outcome has not been extensively examined. Among the signal transducer and activator of transcription (STAT) proteins, Stat3 activity is frequently up-regulated in many human tumors. Various lines of evidence have established a causal role for aberrant Stat3 activity in malignant transformation and provided validation for its targeting in the development of small-molecule inhibitors as novel cancer therapeutics. We report here that platinum-containing compounds disrupt Stat3 signaling and suppress its biological functions. The novel platinum (IV) compounds, CPA-1, CPA-7, and platinum (IV) tetrachloride block Stat3 activity in vitro at low micromolar concentrations. In malignant cells that harbor constitutively activated Stat3, CPA-1, CPA-7, and platinum (IV) tetrachloride inhibit cell growth and induce apoptosis in a manner that reflects the attenuation of persistent Stat3 activity. By contrast, cells that do not contain persistent Stat3 activity are marginally affected or are not affected by these compounds. Moreover, CPA-7 induces the regression of mouse CT26 colon tumor, which correlates with the abrogation of persistent Stat3 activity in tumors. Thus, the modulation of oncogenic signal transduction pathways, such as Stat3, may be one of the key molecular mechanisms for the antitumor effects of platinum (IV)–containing complexes.

A method for real-time nondestructive monitoring of small molecules diffusion in polymeric films was developed. The method was based on detection of a fluorescent tracer eluting from the investigated polymer film into the solution in which this film was immersed. The kinetics of the tracer elution, monitored by the increase in solution fluorescence intensity, was used to deduce tracer diffusivity in polymer film. The data were treated using a straightforward mathematical model, describing diffusion from an infinite plane of a certain thickness immersed into a finite solvent bath. Fluorescent 7-diethylamino-4-methyl coumarin was used as a tracer. The diffusion of this tracer within plasticized poly(methy1 methacrylate) and styrene-isoprene-styrene block copolymer matrices was monitored. The diffusion coefficients equal to 2 X lo-' cm2/s and 1 X lo-' cm2/s, respectively, were obtained.

Factor analysis has been used to resolve the overlapping XPS spectra obtained in the x-ray-induced transformation of Pt(en)2(OH)2Cl2 to Pt(en)2Cl2. This is achieved without prior knowledge of the data set nor the establishment of any initial curve fitting criteria.

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