Functional-characterization of developing tumor vascular system and drug delivery (review).

This review summarizes our recent experiments on the process of tumor vascularization and character of tumor vessels. By vitalscopic observation with transparent chambers in rats, we found that the sites where tumor vessels originated were usually terminal portions of terminal arterioles and that an intricate tumor vascular network was constructed from incorporated preexisting vessels and newly formed vessels by three different modes, i.e., sprouting, cross-connecting and splitting. Observation and hydrogen clearance studies showed that tumor blood flow changed remarkably during the development of the tumor vascular network. At an early stage of tumor growth, there were some regions of high flow in the tumor. At an advanced stage, however, there was a rapid increase in low-flow or no-flow areas which were resistant to access of anticancer drugs and oxygen. Angiotensin II-induced hypertension produced a several-fold increase in tumor blood flow without increasing tissue blood flow of normal tissues. These good conditions for drug delivery to tumor tissue are able to enhance therapeutic effects of chemotherapy, irradiation, antibody and photodynamic therapy.