KC) function has been shown to modulate the growth of An increasing number of hepatic resections are being experimental liver metastases. 7-8 performed as potentially curative surgery for malignant Interferon gamma (IFN-g) is a glycoprotein produced by T liver neoplasms. Hepatectomy and subsequent liver relymphocytes and natural killer cells, whose functions include generation produce a local environment that enhances inhibition of viral replication and upregulation of class I and growth of microscopic residual tumor. To determine if II major histocompatibility complex antigens. 9 This cytokine pretreatment with murine interferon gamma (IFN-g) also enhances the efficiency of macrophage-mediated killing can protect against such enhanced tumor growth, Bufand lymphocyte activity in vitro. IFN-g has a low toxicity falo rats were randomized to receive a 3-day treatment profile and already has been used in clinical studies. [13][14] The of IFN-g (50,000 U/qD intraperitoneally) or saline.
current experiments were performed to determine if IFN-g Groups then underwent intrasplenic injection of 10 6 may be useful in preventing hepatectomy-enhanced tumor Morris hepatoma cells, followed 1 hour later by sham growth and to decipher the potential mechanisms involved. (control) or partial hepatectomy (PH) of 70%. PH significantly enhanced tumor growth within the liver (control, MATERIALS AND METHODS 8 { 3 nodules per liver; PH, 73 { 12 nodules per liver; P õ .001). This enhancement was attenuated by prior Animals. Specific pathogen-free male Buffalo rats (Harlan administration of IFN-g IFN-g/PH, 16 { 3; P õ .001 vs. Sprague Dawley, Indianapolis, IN, or the National Cancer Institute) PH). Growth factor release and liver regeneration were were housed in individual cages in a temperature-(22ЊC) and humid- ity-controlled room with an automatic day/night cycle of 12 hours not affected significantly by pretreatment with IFN-g. each. Animals were provided rodent chow (P.M.I. Mills, St. Louis, The effect of IFN-g on tumor growth is associated with MO) and water ad libitum. Food consumption and body weight were a significant enhancement of Kupffer cell (KC)-mediated measured daily. All animals received care in compliance with Memotumoricidal activity (percentage of specific lysis, 55 { rial Sloan-Kettering Cancer Center's Institutional Animal Care and 10% control, 78 { 11% IFN-g; P õ .01) but not lymphocyte-Use Committee guidelines. mediated tumoricidal activity. Because microscopic re-Tumors. A syngeneic tumor, Morris hepatoma McA-RH7777
sidual disease may be present after hepatectomies for (ATCC no. CRL 1601), was sequentially passaged subcutaneously cancer, IFN-g may be a useful agent in retarding growth in Buffalo rats. For splenic injections, tumor cell suspensions were of residual tumors. (HEPATOLOGY 1996;24:374-379.) prepared by excising tumor from the previous host, cutting it into 2-5 mm pieces, and incubating it in 5 to 10 mL of trypsin (0.125% trypsin/0.125% ethylenediaminetetraacetic acid in phosphate-buf-Abbreviations: PH, partial hepatectomy; KC, Kupffer cell; IFN-g, interferon gamma; neally prior to skin closure with wound clips. NS, normal saline; bFGF, basic fibroblast growth factor; TGF-b, transforming growth factor Splenocyte Isolation. Groups (n Å 8 per group) were injected intrab.
peritoneally with 100 mL of IFN-g or NS for 3 days. Animals then