Analysis of Mammalian Tumor Vascularization in the Development of a Therapy to Prevent Metastasis

摘要

In this investigation the use of thrombin as both a tumor growth inhibitor and anti-metastatic agent is studied using transplantable renal, adenocarcinoma and rhabdomyosarcoma. The administration of one bolus injection of thrombin to the tumor necrotic region at six weeks post-implantation (pre-metastatic) prolongs the time to metastasis to approximately twenty weeks post-implantation (or roughly double the life expectancy following tumor implantation) depending on the tumor diameter at the time the thrombin is delivered. In addition, the growth rate of the primary tumor is considerably decreased probably due to vascular thrombosis of the tumor vasculature leading to increased ischemia and subsequent tumor necrosis. The results of the morphological examination and the success of the thrombin therapy provide evidence for the existence of a radially directed open vessel pathway in the metastatic process. From the results of the students' t-test on the morphological data one can assert that inward directed radial tumor vasculature exists. Two classes of these inward radial tumor vessels are found: Class 1 consists of vessels that are not active mitotically but are open-ended; Class 2 consists of vessels that are active mitotically (i.e., growing) but are closed-ended; indicating the growth of new tumor vasculature. Class 1 tumor vessels may provide the entrance into which thrombin can permeate and fill the entire tumor parenchyma resulting in both tumor toxic and anti-metastatic effects. (30 refs., 24 figs., 8 tabs.). (ERA citation 11:005627)