Biomaterial-associated thrombosis: roles of coagulation factors, complement, platelets and leukocytes

Delivery of molecular and cellular medicine to solid tumors

Extraordinary advances in molecular biology and biotechnology have led to the development of a vast number of therapeutic anti-cancer agents. To reach cancer cells in a tumor, a blood-borne therapeutic molecule, particle, or cell must make its way into the blood vessels of the tumor and across the vessel wall into the interstitium, which it then must migrate through. Unfortunately, tumors often develop in ways that hinder these steps. The goal of research in this area is to analyze each of these steps experimentally and theoretically and integrate the resulting information into a unified theoretical framework. This paradigm of analysis and synthesis has fostered a better understanding of physiological barriers in solid tumors and aided in the development of novel strategies to exploit and/or overcome these barriers for improved cancer detection and treatment.

Transport of molecules, particles, and cells in solid tumors.

For a systemically administered therapeutic agent to reach neoplastic cells, it must enter the blood circulation, cross the vessel wall, move through the extracellular matrix and avoid getting cleared by the lymphatics. In tumours, each of these barriers is abnormal, changes with space and time, and depends on host-tumour interactions. Intravital microscopy has provided unprecedented molecular, cellular, anatomical and functional insights into these barriers and has revealed new approaches to improved detection and treatment.

C. Ohkubo

Papers

Selectin- and integrin-mediated T-lymphocyte rolling and arrest on TNF-alpha-activated endothelium: augmentation by erythrocytes.

Leukocyte rolling increases with age.