To investigate the influence of surgical stress on fibroblast proliferation, serum samples were collected from 12 patients within 1 week after they had undergone gastrointestinal surgery, and the effect of these samples on the growth of fibroblasts from neonatal mice were evaluated by an in vitro assay. In addition, the course of the postoperative plasma levels of the stress-induced hormones, adrenaline, noradrenaline, and cortisol, and the direct effects of these substances on the proliferation of fibroblasts, were also analyzed. The sera collected from patients on the 1st, 3rd, and 7th postoperative day had a significant antiproliferative effect on the growth of fibroblasts. The evaluation of the levels of plasma catecholamines (adrenaline and noradrenaline) and cortisol revealed elevated postoperative concentrations of these substances in three patients, and the peaks were seen on the 1st or 3rd postoperative day. Furthermore, the growth of cultured fibroblasts was inhibited when each of these substances was added to the medium at a concentration comparable to the level found in the postoperative sera. These results suggest that adrenaline, noradrenaline, and cortisol may thus be among the circulating fibroblast growth inhibitors in postoperative patients and that surgical stress affects the formation of granulation in an inhibitory manner through the elevation of these stress-induced substances.

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In clinically hyperthermia and irradiation therapy for malignant neoplasms are known that they have antiproliferative activity and cell death (including apoptosis) inducing activity. However not only mechanisms of cell death induction but treatment effects of them still have been unclear. In this time we showed that cell cycles from G0/G1 phase to S-G2/M phase were delayed by hyperthermia and G2/M phase accumulation were caused immediately by irradiation. And we also demonstrated that the combination treatments of hyperthermia and irradiation induced synergistic antiproliferative effects and strong effects of cell death to human esophageal carcinoma cell lines. Although treatments of hyperthermia and irradiation were mild individually, combination treatment of hyperthermia and irradiation were useful for esophageal carcinoma treatment.