Keiichi Muraoka

Effects of Natural Antioxidants on the Activation of Transcription Factor NF-κB and p53

Although various natural antioxidants, such as vitamin E, flavonoids, and polyphenols, have been reported to show antiinflammatory and anticarcinogenic activities, it is not clear how they exert these activities. To clarify the mechanisms involved, we studied effects of these natural antioxidants on the activation of transcription factors activated by inflammatory or anticancer agents. One such factor is NF-κB, which is involved in the regulated expression of various inflammation-related genes and is activated by a variety of noxious inflammatory or environmental stresses. We first studied the effects of those antioxidants on interleukin-1 (IL-l)-induced NF-κB activation. Many natural flavonoids and tea polyphenols inhibited IL-1-induced NF-kB activation, the most typical being antioxidant N-acetyl-cysteine (NAC). Although vitamin E enhanced IL-1-induced NF-κB activation, it inhibited hypoxia-induced NF-κB activation. Another transcription factor activated by similar noxious stress is p53, which plays an important role in cell cycle checkpoint control. Although many anticancer drugs, including mitomycin C, are potentially radical-generating agents, antioxidants such as NAC and vitamin E did not inhibit but, rather, enhanced mitomycin C-induced p53 promoter activation. Thus our study indicates that complex mechanisms are involved in the antiinflammatory and anticarcinogenic activities of these natural antioxidants.

Continuous Hyperthermic and Normothermic Peritoneal Perfusion for the Prevention of Peritoneal Recurrence of Gastric Cancer — A Randomized Control Study

We had reported advantage of continuous hyperthermic peritoneal perfusion (CHPP) for the prevention of peritoneal recurrence after surgery for gastric cancer in a historical control study. We performed CHPP (CHPP group, n=22) or continuous normothermic peritoneal perfusion (CNPP group, n=18) combined with cisplatin and mitomycin C for the prevention of peritoneal recurrence. The survival curve of the CHPP group was significantly better than of the CNPP group in log-rank test (p<0.01). This fact showed that not only intraperitoneal perfusion combined with chemotherapy (CNPP) but also intraperitoneal hyperthermia(CHPP) are effective procedures for prevention of peritoneal recurrence.