1. Effect of preoperative administration of methylpredonisolone and ulinastatin on tumor cell metastasis after surgical stress.
- Author
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Momosaki K, Ishibashi N, Yoshida S, Muraoka T, Tanaka K, Iwakuma N, Oka Y, Kaibara A, Akagi Y, and Shirouzu K
- Subjects
- Administration, Intravenous, Animals, Antineoplastic Agents administration & dosage, Ascites pathology, Cell Adhesion drug effects, Cell Line, Tumor, Cytokines blood, Drug Administration Schedule, Glucocorticoids administration & dosage, Glycoproteins administration & dosage, Immunocompromised Host, Inflammation Mediators blood, Liver Neoplasms immunology, Male, Methylprednisolone administration & dosage, Neoplasm Transplantation, Preoperative Care, Rats, Time Factors, Antineoplastic Agents pharmacology, Glucocorticoids toxicity, Glycoproteins pharmacology, Laparotomy adverse effects, Liver Neoplasms pathology, Liver Neoplasms prevention & control, Liver Neoplasms, Experimental prevention & control, Liver Neoplasms, Experimental secondary, Methylprednisolone toxicity
- Abstract
Using a rat laparotomy stress model, we conducted a comparative analysis of postoperative organ metastasis after administration of ulinastatin (UTI) or methylprednisolone (MP), which have an inhibitory effect on cytokine production. The subjects were classified into 4 groups: 1) minimal laparotomy group (C group), 2) major laparotomy group (L group), 3) preoperative MP intravenous administration + major laparotomy group (MP group), and 4) preoperative UTI intravenous administration + major laparotomy group (UTI group). Either MP or UTI was administered intravenously before surgery, and RI-labeled cells were injected into the portal vein immediately after laparotomy to collect tissue specimens in order to measure radiation dosage. Then, the concentrations of serum IL-2 and IL-6, liver interleukin 1 beta (IL-1β) and interleukin 10 (IL-10), and liver E-selectin were measured. In addition natural killer cell, (NK cell) activation and neoplastic nodules on the liver surface at 3 weeks after surgery were also measured. The adhesion rate of malignant cells to the liver was higher in the L group than in the C group, higher in the MP group than the L group, and lower overall in the UTI group. The concentration of IL-1β and IL-6 were decreased in the MP and UTI groups compared to the L group. IL-2 was decreased significantly in the MP group compared with the C and L groups. E-selectin expression level decreased in the UTI group compared with the L group. NK cell activation decreased in the MP group compared with the C group and L group, but no differences were observed between the UTI and L groups. The number of tumor nodules on the surface of the liver increased in the MP group compared with the L group, and decreased in the UTI group compared with the L group. Postoperative alleviation of invasive reaction was suggested in both the MP and UTI groups. However, preoperative administration of MP increased metastasis while that of UTI inhibited metastasis. MP was considered to have decreased anti-tumor immunocompetence and promoted metastasis, while UTI was considered to have inhibited the expression of adhesive molecules and decreased metastasis.
- Published
- 2014
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