Decrease of Metastases of Carcinosarcoma Walker 256 with Irradiation and Heparin or Fibrinolytic Agents

Abstract

Cancer cells in the circulating blood of patients with malignant tumors were first demonstrated by Ashworth (4) almost one hundred years ago (1869). Pool and Dunlop (19) in 1934 observed unusual cells in the peripheral blood in cases of advanced malignant disease, and in 1955 Engell (12) reported the presence of cancer cells in the peripheral blood of patients with resectable and unresectable neoplasms. There have been many more recent reports. With this evidence and the observation that venous invasion frequently is dcmonstrated in microscopic sections of malignant tumors (5, 11), it has been presumed that cancer cells may be spilled from the primary lesion into the circulating blood. An increase in the number of cancer cells in the venous blood draining the tumor may be noted (6, 22) at the time of examination (17), at biopsy (23), and during surgical procedures (10). Not all of these cancer cells become metastases. Some may lie dormant in the tissues for years (13), while others are destroyed in the circulation or in the tissues. Surgical procedures have been adapted to minimize the spread of cancer by this means (9), and chemotherapeutic agents have been introduced as a prophylactic measure in clinical trials. Nitrogen mustard and ThioTEPA have been reported to be effective in reducing the number of free floating cancer cells (8, 24). We felt it was necessary to learn more about the mechanism of metastases before using toxic agents in postoperative patients. On the assumption that clumping and fixation of cells in the capillaries would be necessary to produce metastases, we undertook to determine the effect on metastatic growth of altering the clotting mechanism. Human fibrinolysin and heparin in effective doses were found to decrease pulmonary metastases of the Brown-Pearce (7) and the VX₂ carcinoma of the rabbit (7) and the Walker 256 carcinosarcoma of the rat (1, 14). The present study was undertaken to determine the effect of these agents combined with methods which would partially devitalize the cancer cells. Radiation is known to devitalize or destroy cells depending upon the dose delivered. The rate of metastasis of tumor cells treated with sufficient irradiation to devitalize but not destroy them prior to implantation or injection, with and without anticoagulants, is the subject of this paper. Materials and Methods Tumor Cells For this experiment 1054 rats were used. 1. The Walker 256 carcinosarcoma cells were obtained from 20 donor rats bearing the ascitic form of the tumor, which has been carried continuously in this laboratory for several years. The tumor was permitted to grow until the abdominal cavity of each animal contained 20 to 30 ml. of ascitic fluid. The fluid was then withdrawn and diluted with saline until the count was 100,000 cells/ml. Control tumor cells were obtained from non-irradiated animals.