The main goal of the research activities of the Investigative and Treatment Division is to develop new strategies of cancer diagnosis and treatment based on a better understanding of the biology of cancer tissues and the interaction between cancer and the host. Improvement of pre-existing modalities of cancer diagnosis and treatment is also pursued.
The objective of the drug delivery system (DDS) in cancer chemotherapy is to determine methods by which anticancer agents selectively target solid tumors. Two main concepts constitute selective tumor targeting, active targeting and passive targeting. The former involves monoclonal antibodies or ligands to tumor-related receptors which can target the tumor by utilizing specific binding ability between an antibody and an antigen or between the ligand and its receptor. The latter system can be achieved by the so-called enhanced permeability and retention (EPR) effect. This EPR effect in solid tumor tissue was named based on the following pathophysiological characteristics: (a) hypervasculature; (b) incomplete vascular architecture; (c) stimulation of extravasation within the cancer by several vascular permeability factors; and (d) slight drainage of macromolecules and particulates. Macromolecular anticancer agents such as liposomal or micellar drugs have long plasma half-lives because they are very large to pass through normal vessel walls unless they are trapped by the reticuloendothelial system in various organs. Such macromolecular agents can diffuse out of tumor blood vessels, reach the solid tumor tissue effectively and be retained for a long period due to the EPR effect. In this regard, polymeric micelles have been expected to increase drug accumulation in tumor tissues through the EPR effect, as well as incorporate various kinds of drugs into their inner core by chemical conjugation or physical entrapment with relatively high stability. Importantly, the size of the micelles can be controlled within the diameter range of 20 to 100 nm, and this ensures that the micelles do not pass through normal vessel walls. This therefore suggests a reduction in the incidence of side effects due to the reduced volume of drug distribution in normal tissues. At present, several anticancer agent-incorporating micelle carrier systems are under clinical evaluation. Phase 1 studies of a CDDP-incorporating micelle (NC-6004) and an SN-38-incorporating micelle (NK012) are currently underway. A phase 2 study of a PTX-incorporating micelle (NK105) against stomach cancer is also on-going (110-111). NK012, which combines enhanced distribution with prolonged sustained release of SN-38 within tumors, is ideal for the treatment of hypovascular tumors such as pancreatic cancer since the antitumor activity of SN-38 is time-dependent (112). In other tumors such as colorectal and renal cancer (113), glioma, and gastric cancer (114), NK012 has shown significant superior antitumor activity and induced longer survival than CPT-11. In a glioma orthotopic xenograft model, both NK012 and CPT-11 appeared capable of effectively extravasating from the blood brain tumor barrier but not from normal brain vessels. In addition to anticancer agent delivery systems, a local gene delivery system in combination with ultrasound has shown promise as a candidate for new oncological treatment (115-116).
Colon cancer is almost 100% curable by operation if detected early Thus, it is usually included in an early cancer screening schema, and many examination methods for its early detection have been developed. Recently, a new method has been developed in which exfoliated colorectal cancer cells can be effectively isolated from naturally voided feces. The cell recovering method and apparatus based on our invention can simplify the cell recovery operation and allow cancer cells in stool to be recovered stably and efficiently, thereby providing a high determination accuracy (117, 118, 119).
● Y. Matsumura ●
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