Frequency of killer cell immunoglobulin-like receptors (KIRs) in Korean patients with chronic HCV infection.

Natural killer (NK) cells play an important role in innate immunity, especially in the response to viral infections, such as hepatitis C virus (HCV). Killer cell immunoglobulin-like receptors (KIRs) are the primary receptors of NK cells that mediate innate immunity. KIRs are also involved in acquired immunity, because some KIRs are expressed on the surface of certain subsets of T cells. In this study, the frequency of KIR genes, HLA-C allotypes, and combinations of KIR genes with their HLA-C ligands were evaluated in two different groups of the Korean population: controls and patients with chronic HCV infection. The study population consisted of 147 Korean patients with chronic HCV infection. The frequency of KIR2DS2 in patients with chronic HCV infection was 9.5% which was significantly lower than 19.5% of the control (P < 0.01). However, there were no significant differences in the frequency of other KIR genes, HLA-C allotypes or different combinations of KIR genes with their HLA-C ligands. This study can contribute to the further prospective study with a larger scale, suggesting the assumption that KIR2DS2 might aid in HCV clearance by enhancing both the innate and acquired immune responses of people in Korea.

Beneficial effect of metronomic chemotherapy on tumor suppression and survival in a rat model of hepatocellular carcinoma with liver cirrhosis.

PURPOSE: Recent studies have demonstrated that frequent, low-dose metronomic (MET) dosing of cytotoxic agents may not only be as efficient as conventional maximum tolerated dose (MTD) chemotherapy but also less toxic. In this study, we investigated the therapeutic effect and safety of MET chemotherapy using cyclophosphamide (CTX) in rats with chemically induced hepatocellular carcinoma (HCC). METHODS: Rats received weekly intraperitoneal (i.p.) injections of diethylnitrosamine during 16 weeks for induction of HCC. The rats were divided into three groups: MTD group received 40 mg/kg CTX i.p. injection on days 1, 3, and 5 of a 21-day cycle; Control and MET groups received saline and 20 mg/kg CTX i.p. injection twice a week, respectively. The growth-modulating effects and overall survival were compared between the groups. Anti-angiogenic effects were evaluated by a measurement of endothelial cell and VEGFR-2 expression. RESULTS: At 6 weeks of therapy, MTD and MET chemotherapy resulted in a significant reduction in tumor number and size compared with Control group. MET chemotherapy showed more prolonged survival than MTD chemotherapy and Control groups (P < 0.05). MET chemotherapy resulted in a significant decrease in both the micro-vessel density and endothelial proliferation index (P < 0.01). Furthermore, MET chemotherapy led to a greater decrease in VEGFR-2 expression at the mRNA and protein levels (P < 0.01). CONCLUSIONS: MET scheduling not only exhibits anti-tumor and anti-angiogenic effects, but also prolongs survival without major toxicities in a rat model of HCC. Our results suggest that MET chemotherapy has a high therapeutic value and should be considered for future clinical trials.