The Surgical Metabolism Section has completed a clinical research project evaluating the efficacy of neoadjuvant chemotherapy for patients with locally advanced gastric adenocarcinoma. The results indicate that a response to neoadjuvant fluorouracil-based therapy may be associated with decreased levels of total thymidylate synthase before therapy and free thymidylate synthase after a brief exposure to fluorouracil. The quantification of thymidylate synthase protein expression may now provide a method to select patients for this therapy. The Surgical Metabolism Section has conducted clinical research projects evaluating the feasibility, toxicity, and efficacy of continuous hyperthermic peritoneal perfusion using high-dose cisplatin with or without tumor necrosis factor for patients with peritoneal carcinomatosis. The results to date indicate that high-dose intraperitoneal cisplatin is well tolerated in the setting of hyperthermic perfusion and that a favorable pharmacokinetic profile is observed. The laboratory has conducted in vitro and in vivo studies to develop new strategies to treat intraperitoneal carcinomatosis. The intraperitoneal administration of cisplatin and tumor necrosis factor in nude mice with peritoneal carcinomatosis from a human gastric cancer will significantly improve survival compared to animals treated with either agent alone. Tumor levels of cisplatin are significantly increased in the presence of TNF. The laboratory has been evaluating the cellular interactions between cancer cell lines and monocytes or macrophages. Constitutively expressed tumor products including cytokines such as leukemia inhibitory factor or IL-6 will upregulate macrophage production of interleukin-lO and may explain the cellular basis of altered immune status in the cancer bearing host. The laboratory has evaluated the regulation of OB gene expression in adipose tissue during acute and chronic inflammatory diseases and in response to various cytokines such as TNF and IL-1. Because anorexia is a hallmark manifestation of cancer cachexia and other acute inflammatory diseases. The laboratory has investigated the regulation of this gene which encodes a protein that is a satiety factor.
