We report herein an unusual case of metachronous triple cancers of the sigmoid colon, stomach, and esophagus. A 60-year-old man was initially admitted to our hospital for investigation of occult fecal blood. This was found to be caused by sigmoid colon cancer which was resected in July 1985 (T3, N0, M0; Stage II). A follow-up endoscopy performed in 1990 showed early gastric cancer, and a gastrectomy was performed in August 1990 (Tis, N0, M0; Stage 0). Another endoscopic examination performed as follow-up in 1993 revealed early cancer of the remnant stomach, and all the remnant stomach was surgically resected in March 1993 (Tis, N0, M0; Stage 0). He presented again in December 1996, complaining of discomfort in the chest which was found to be caused by cancer of the middle thoracic esophagus. Although surgery was considered necessary, the patient refused to undergo any further operations. Instead, radiation was administered from January 1997. An endoscopy after the completion of radiotherapy confirmed that the cancer had almost disappeared; however, it started to grow again from the beginning of 1998. He was hospitalized due to esophageal stenosis in April 1998, and died of carcinomatous cachexia in September of the same year.

Objective: An important issue in cancer therapy is to investigate the mechanism for cellular sensitivity to anticancer agents such as cisplatin. Cisplatin is one of the DNA-damaging agents and several factors including p53 are related to the sensitivity to cisplatin in cancer. Protein kinase C (PKC) δ is known as a positive regulator for cisplatin-induced cell death. In our present study, we examined whether overexpression of PKCδ and p53 increases the sensitivity of the human gastric cancer cell line, MKN28, which has a mutation of p53 gene, to cisplatin. Methods: Cell viability and DNA content were measured in MKN28 with adenovirus-mediated expression of PKCδ and p53 after exposure to cisplatin. In addition, the active form of caspase-3 was detected by Western blotting. Results: Overexpression of exogenous PKCδ did not induce cell death in MKN28 but inhibited cell growth at 1 µg/ml cisplatin as compared to that by cisplatin alone. Moreover, overexpression of both wild-type p53 and exogenous PKCδ in MKN28 increased cisplatin-induced cell death in MKN28. Conclusion: These results suggest that PKCδ, in cooperation with p53, possibly regulates cisplatin-induced caspase-3-mediated cell death in gastric cancer.