Antitumor effects of residual tumor after cryoablation: the combined effect of residual tumor and a protein-bound polysaccharide on multiple liver metastases in a murine model.
Cryoablation is a low-invasive surgical treatment for malignant tumors. It may induce an immunological response leading to the eradication of distant metastases or alternatively it might promote the growth of residual tumors. In this paper we confirm the occurrence of both phenomena and we describe the preventive effect of a protein-bound polysaccharide preparation. Metastatic liver tumors were produced in BALB/c mice by the intrasplenic inoculation of colon 26 cells and cryoablation was carried out using liquid nitrogen (-170 degrees C) applied by a contact method. The value of combining cryoablation with administration of the polysaccharide preparation in the prevention of growth of residual tumors was investigated. It was shown that the number of metastatic liver nodules and the size of the primary tumor at the site of inoculation in the spleen were significantly lower when the volume that was frozen was small. The production by splenocytes of the tumor necrosis factor TNF-alpha, interferon INF-gamma, and the interleukins IL-4 and IL-10 increased significantly after freezing and thawing of the tumor tissue. The polysaccharide treatment significantly reduced the production of IL-4 and IL-10 following cryoablation; the production of TNF-alpha and INF-gamma was slightly promoted; the natural killer and cytotoxic T-cell activities of splenocytes were slightly enhanced. It was concluded that the polysaccharide preparation was beneficial by suppressing IL-4 and IL-10 production and might inhibit the growth of residual tumor that is sometimes induced by large-volume cryoablation.
Urano
Masato
M
Department of Tumor and General Surgery, Gifu University School of Medicine, 40 Tsukasa-machi, Gifu 500-8705, Japan.
Tanaka
Chihiro
C
Sugiyama
Yasuyuki
Y
Miya
Kiichi
K
Saji
Shigetoyo
S
D000818:Animals; D002478:Cells, Cultured; D003452:Cryosurgery / Q000379:methods; D016207:Cytokines / Q000096:biosynthesis; D003602:Cytotoxicity, Immunologic; D006128:Growth / Q000187:drug effects; D007155:Immunologic Factors / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000517:prevention & control / Q000556:secondary* / Q000601:surgery*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D018365:Neoplasm, Residual / Q000503:physiopathology*; D009929:Organ Size; D011509:Proteoglycans / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013160:Splenic Neoplasms / Q000473:pathology
D016207:Cytokines; D007155:Immunologic Factors; D011509:Proteoglycans; C010770:polysaccharide-K