Influences of operative stress on nonspecific cell-mediated immunity and on liability to tumor metastasis and preventive effects thereon of a nonspecific immunopotentiator OK-432 were examined. Syngeneic female SD rats were inoculated SC with 200 mg of a transplantable mammary carcinoma MRMT-1 at the dorsal flank. After 2 weeks the tumor was surgically excised simply or combined with 30-min laparotomy. It was revealed by follow-up examination that the laparotomy stress significantly increased incidence of postoperative lung metastasis. It was found that PHA-induced blastogenesis of peripheral lymphocytes was markedly reduced in the early period following laparotomy. Preoperative or post-operative (especially the former) administration of OK-432 was effective for preventing both the postlaparotomy facilitation of lung metastasis and the postlaparotomy reduction in PHA lymphoblastogenesis.
Immunologic merits and demerits of splenectomy were studied using a rat's experimental tumor. When splenectomy was done on day - 14, 2, or 14 of tumor inoculation, subsequent tumor growth was inhibited, but when it was done on day 7, tumor enhancement was observed. On day 2, cpm values of phytohemagglutinin (PHA)-induced blastogenesis of splenocytes was lower than in normal rats, on day 7 they significantly increased as compared with day 2, and on day 14 they significantly decreased as compared with day 7. Stimulation index (SI) ratio of PHA-induced blastogenesis and natural cell-mediated killing (NK) activity were also investigated using splenocytes, thymocytes, and peripheral lymphocytes. The results indicated that immunological competency of splenocytes of tumor bearers was reduced in the early, late, and final tumor-bearing periods, while it was increased in the middle tumor-bearing period. Tumor growth following splenectomy was considered to be controlled by these changes in immunological competency of splenocytes.
5-week-old syngeneic female SD rats were inoculated subcutaneously at the dorsal flank with 200 mg of a metastasizing rat’s mammary tumor, MRMT-1. A significantly higher incidence of lung metastasis was observed in the cases in which tumor excision on day 14 was accompanied by 30 min laparotomy than in the cases of simple tumor excision. PHA lymphoblastogenesis on day 17 was significantly lower in the cases of tumor excision plus laparotomy on day 14 than in the cases of simple tumor excision. Winn’s assay using splenocytes revealed a postoperative enhanced suppressor activity in the cases undergoing laparotomy stress. Possible participation of the raised suppressor activity to facilitation of metastasis was discussed.
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