The mechanism of tumor cell killing by OXI4503 was investigated by studying vascular functional and morphological changes post drug administration. SCID mice bearing MHEC5‐T hemangioendothelioma were given a single dose of OXI4503 at 100 mg/kg. Tumor blood flow, measured by microsphere fluorescence, was reduced by 50% at 1 hr, and reached a maximum level 6–24 hr post drug treatment. Tumor vascular permeability, measured by Evan's blue and hemoglobin, increased significantly from 3 hr and peaked at 18 hr. The elevated tumor vessel permeability was accompanied by an increase in vascular endothelial growth factor (VEGF) from 1 hr post drug treatment. Immunohistochemical staining for CD31 and laminin showed that tumor blood vessels were affected as early as 3 hr but more prominent from 6 hr. From 12 hr, the vessel structure was completely destroyed. Histopathological and double immunohistochemical staining showed morphological change and induction of apoptosis in endothelial cells at 1–3 hr, followed by tumor cell necrosis from 6–72 hr. There were no statistically significant changes of Evan's blue and hemoglobin contents in liver tissue over the time course. These results suggest that OXI4503 selectively targets tumor blood vessels, and induces blood flow shutdown while it enhances tumor blood vessel permeability. The early induction of endothelial cell apoptosis leads to functional changes of tumor blood vessels and finally to the collapse of tumor vasculature, resulting in massive tumor cell necrosis. The time course of the tumor vascular response observed with OXI4503 treatment supports this drug for development as a stand alone therapy, and also lends support for the use of the drug in combination with other cancer therapies.

A variety of organic liquids can be immobilised using certain 4-tert-butyl-1-arylcyclohexanol derivatives (BACOl). Only the isomers with axial aryl groups are active as gelling agents. The BACOl–hydrocarbon systems have been characterised with respect to their rheological properties under shear. The gels are viscoelastic solids with high elastic shear moduli (G′≈70350 Pa at C≈2.2 wt.% in dodecane) and high yield stresses (σ≈620 Pa). A 3D network with high cohesive energy and long lifetimes of the related structures is in thermal equilibrium with the surrounding solution. Diffraction experiments have characterised the crystallinity of the gel networks made up of assemblies of bimolecular BACOl associations (d≈14.3 Å). Xerogels exhibit a mesomorphic organisation with a 76 Å repeating unit. Phase diagrams have been determined as a function of the solvent and gelator types and the related thermodynamic parameters were deduced. IR spectroscopy has demonstrated that H-bonding is responsible for the aggregation of the BACOl molecules.