Yoshiaki Kanaya

Effects of experimental chemoendocrine therapy with a combination of a pure antiestrogen and 5-fluorouracil on human breast cancer cells implanted in nude mice.

The antitumor effects of an experimental chemoendocrine therapy combining a new pure antiestrogen ICI 182780 and 5-fluorouracil (5-FU) were studied on MCF-7 human breast cancer cells implanted in nude mice. ICI 182780 had a dose-dependent antitumor activity, which was potentiated by the concomitant use of 5-FU. When compared with the control group, the estrogen receptor (ER) level in the ICI 182780 group was lower and that in the combination group was markedly lower. Cell cycle analysis by flow cytometry (FCM) resulted in a lower percentage of S-phase cells (%S) in the treated mice. No significant difference was observed in the 5-FU concentrations in tumor cells, while the 5-FU content in RNA was significantly higher in the combination group. The changes in free thymidylate synthetase (TS) concentration indicated TS synthesis after the administration of 5-FU to be more greatly suppressed in the combination group than in the 5-FU group. These results suggest that ICI 182780 and 5-FU exert their combination effect mainly on ER-positive cells, and that the suppression of TS synthesis in tumor cells and the potentiation of the 5-FU-induced metabolic dysfunction of RNA are thus involved in the mode of action of this combination therapy.

Effect of Combined Therapy with the Antiestrogen Agent Toremifene and Local Hyperthermia on Breast Cancer Cells Implanted in Nude Mice

PurposeWe evaluated the effects of combined treatment with the antiestrogen agent toremifene (TOR) and local hyperthermia (LHT) on the MCF-7 breast cancer cell line.MethodsBALB/c mice implanted with MCF-7 cells were divided into six treatment groups: a control group, a TOR30 group (given 30 mg/kg/day), a TOR120 group (given 120 mg/kg/day), an LHT group (43.5°C), a TOR30 + LHT group, and a TOR120 + LHT group. The effects of the treatments on tumor cells, estrogen receptor (ER) expression, and cell cycle kinetics were measured after 21 days. We calculated the apoptotic index and vascular density inside the tumors and evaluated the efficacy of the transmigration of TOR into the tumors.ResultsThe antitumor effects were significantly greater in both combined therapy groups than in any of the single therapy groups. Estrogen receptor expression was weaker in the combined therapy groups than in the single therapy groups, and there were more G0/G1-phase cells and fewer S-phase cells in both combined therapy groups than in the single therapy groups. The apoptotic index was increased and the tumor vascular density was decreased in the combined therapy groups.ConclusionsWe attributed the effects of this combined therapy to the induction of apoptosis, the decrease in vascular density, and the increase and decrease in G0/G1-phase and S-phase cells, respectively, in the tumors.

A rare case of recurrent alpha-fetoprotein-producing gastric cancer without re-elevation of serum AFP.

We report an extremely rare case of recurrent alpha-fetoprotein (AFP)-producing gastric cancer without re-elevation of serum AFP. The patient was a 78-year-old woman with AFP-producing gastric cancer, a rare type of gastric adenocarcinoma. A Borrmann III gastric tumour was surgically resected and AFP-producing gastric cancer was diagnosed based on high levels of serum AFP (705.44 ng/ml) and immunohistochemical examination of the tumour. The serum AFP level decreased to the normal range after resection without any sign of recurrence by imaging, but the patient developed local recurrence of the cancer and died 13 months after surgery. No re-elevation of serum AFP levels was observed after recurrence. Although serum AFP levels are believed to be useful for follow-up in the post-operative period, the possibility that serum AFP levels do not always correlate with the extent of the cancer should be kept in mind.

An Incarcerated Colon Inguinal Hernia That Perforated into the Scrotum and Exhibited an Air-Fluid Level

There are few reports of a transverse colon inguinal hernia; furthermore, an inguinal hernia perforating the scrotum is rare. Here we report the case of a 79-year-old man who died after developing an incarcerated colon inguinal hernia that perforated the scrotum and exhibited an air-fluid level. The patient was referred to our hospital in November 2011 with a complaint of inability to move. Physical examination revealed an abnormally enlarged left scrotum and cold extremities. He reported a history of gastric cancer that was surgically treated more than 30 years ago. His white blood cell count and C-reactive protein level were elevated. Abdominal and inguinal computed tomography revealed that his transverse colon was incarcerated in the left inguinal canal. Free air and air-fluid level were observed around the transverse colon, suggestive of a perforation. The patient and his family refused any surgical intervention; therefore, he was treated with sultamicillin tosilate hydrate and cefotiam hydrochloride. However, he succumbed to panperitonitis 19 days after admission. The findings from this case indicate that the transverse colon can perforate into an inguinal hernia sac.