15-hydroxy-11-alpha-9-alpha-(epoxymethano)prosta-5-13-dienoic-acid and Colonic-Neoplasms

Previous studies have demonstrated that human malignancies can synthesize large amounts of thromboxane. It has also been reported that thromboxane can significantly alter multiple components of physiologic and immunologic function. We investigated the effect of elevated levels of thromboxane on host response to tumor using multiple rat models, and the long acting thromboxane analogue U-46619. Administration of the thromboxane analogue was not found to significantly alter the growth of primary tumors or peritoneal metastases. The analogue was found to significantly decrease mean survival time with a pulmonary metastases model. The thromboxane analogue failed to alter macrophage cytotoxicity, lymphocyte cytotoxicity, T lymphocyte subset numbers, or lymphocyte blastogenic response. Administration of the thromboxane analogue decreased the rate of lymphocyte metabolism of glucose and decreased lymphocyte intracellular adenosine deaminase activity. In conclusion, elevated thromboxane levels do not appear to alter primary tumor growth or host immune function, but do decrease resistance to pulmonary metastases.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Animals; Colonic Neoplasms; Fibrosarcoma; Humans; Immunity, Cellular; Immunity, Innate; Killer Cells, Natural; Lymphocytes, Tumor-Infiltrating; Male; Neoplasm Transplantation; Prostaglandin Endoperoxides, Synthetic; Rats; Rats, Inbred F344; Rats, Inbred WF; T-Lymphocyte Subsets; Thromboxanes