A 60-year-old-man underwent initial resection of a rectal tumor, with a transanal approach, on December 6, 2000. The tumor was diagnosed as a gastrointestinal stromal tumor(GIST) by KIT and CD34 immunohistochemistry. In June 2003, a third recurrence in the rectum was discovered, at the same location as the initial tumor, and he was referred to our hospital. Magnetic resonance imaging (MRI) revealed a tumor 3.0 cm in diameter, compressing the prostate anteriorly. After the oral administration of imatinib mesylate (Gleevec, Glivec) at a dose of 400 mg per day for 3 months, the size of the tumor had decreased to 1.2 cm in diameter. On December 12, 2003, a fourth operation was performed successfully, with a perineal approach, preserving sphincter function. More than 40 months after the fourth operation, neither local recurrence nor distant metastasis was detected. Our strategy of treatment with imatinib allows not only complete excision of the tumor but it also reduces postoperative impediments in patients with recurrent rectal GIST.

The interaction between tumor necrosis factor receptor superfamily, member 4 (OX40) on T cells and the OX40 ligand (OX40L) on antigen-presenting cells (APCs) is a pivotal step for T-cell activation and the promotion of antitumor immunity. However, it is hypothesized that soluble OX40 (sOX40) in blood suppresses T-cell activation by blocking the OX40/OX40L interaction. In the present study, the association between blood sOX40 levels and the clinical characteristics of advanced colorectal cancer (CRC) patients was investigated. Blood was collected from 22 patients with advanced CRC. Blood sOX40 levels were determined by enzyme-linked immunosorbent assay (ELISA). Messenger RNA (mRNA) expression encoding OX40 or cytokines was analyzed by quantitative RT-PCR. Blood sOX40 levels were positively correlated with the blood levels of carbohydrate antigen (CA) 19-9, carcinoembryonic antigen (CEA), C-reactive protein (CRP) and soluble programmed cell death ligand-1 (PD-L1) in patients but negatively correlated with the blood levels of albumin. Blood sOX40 levels were not correlated with the mRNA expression of interferon (IFN)-gamma, interleukin (IL)-6, IL-10 and IL-4 in the peripheral blood mononuclear cells (PBMCs) of the patients and were not correlated with the frequency of programmed cell death-1 (PD-1) expressing CD4 + , CD8 + and CD56 + cells. Notably, according to both univariate and multivariate analyses, high blood sOX40 levels were significantly correlated with a reduced survival time in patients. Although activated Jurkat cells (a human T cell line) exhibited an upregulation of sOX40 production and OX40 mRNA expression, the OX40 mRNA expression of the PBMCs of patients was not correlated with blood sOX40 levels. High blood levels of sOX40 were correlated with a reduced survival time in patients with advanced CRC, possibly associated with the suppression of antitumor immunity by sOX40.

Liver injury by endotoxin given during regeneration following a 70% hepatectomy was examined in Wistar rats. The intravenous administration of endotoxin caused an elevation of the serum GPT level, and severe damage of the remnant liver showing centrilobular necrosis with microthrombi. The highest mortality was induced by the administration of endotoxin to rats 24 h after hepatectomy. Kupffer cells in the regenerative phase of the liver showed an augmented in vitro production of both tumor necrosis factor (TNF) and interleukin-1 (IL-1). The simultaneous administration of heparin and prostagladin E1 (PGE1), which is known to suppress the production of TNF and IL-1, reduced the magnitude of liver injury and the mortality of these rats. The absence of any direct cytotoxic effect of TNF and IL-1 against liver cells suggested that the cytokines, produced by Kupffer cells, play an important but indirect role in the remnant liver injury induced by endotoxin after hepatectomy.

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