Tumor microvasculature response to alternated cold and heat treatment

Vascular injury is an important damage mechanism of cancer treatment modalities such as cryotherapy and hyperthermia. In this study, tumor microvasculature response to locally alternated cold and heat treatment has been studied via microscope observation and histopathological analysis. The tumor vascular permeability to Rhodamine labeled 100nm liposomes at different temperatures was quantitatively studied. Murine mammary carcinoma 4T1 was implanted in the nude mice dorsal skin fold window chamber. Either cold or heat, or the alternated cold and heat treatment was imposed to the mouse tumor inside the window by a thermal chamber. There appeared massive hemorrhage in both the periphery and center of the tumor after the alternated cold and heat treatment. Histopathological analysis indicates severe vessel damage and large necrotic tumor tissue areas. Results of permeability measurements show that the liposome nanoparticles hardly extravasate into the tumor interstitium under normal conditions. But the permeability of the tumor vasculature could be significantly enhanced either by increasing or lowering the local temperature.