Immunomodulation with interleukin-2 impruves antitumor effect of chemotherapy and thermotherapy (CROSBI ID 537755)
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Podaci o odgovornosti
Oršolić, Nada ; Bevanda, Milenko ; Bašić Ivan ; Kujundžić, Milan
engleski
Immunomodulation with interleukin-2 impruves antitumor effect of chemotherapy and thermotherapy
Background/aims: Peritoneal carcinomatosis is prognostically a very bad sign and common cause of death in patients with gastrointestinal and gynecologic tumors. The aim of this study was to explore and compare different models of locoregional immunochemotherapy, hyperthermial intraperitonal chemotherapy (HIPEC) in animal model of induced peritoneal carcinomatosis in mice. Material and methods: CBA mice were injected with mammary carcinoma (MCa) cells intraperitoneally (ip) inducting peritoneal carcinomatosis. In preventional model biological response modifiers (BRM), interleukin-2 (IL-2) at dose of 4.1 x 104 IU/mouse was injected into abdominal cavity seven and three days before injection of tumor cells, respectively. Immediately after the injection of tumor cells, heated saline at 37°C or at 43°C was injected ip (hyperthermia treatment). Following this mice were ip treated with doxorubicin (DOX) 20 mg kg-1, cisplatin (CIS) 10 mg kg-1, mitomicyn (MIT) 5 mg kg-1, 5- fluorouracil (5-FU) 150 mg kg-1 either separately or in combination of them. In therapeutic model cytostatics were injected on day 5 after injection of tumor cells. Hyperthermia treatment was performed immediately before injection of cytostatic drugs. Results: Results showed significant difference in surviving time (engl. increased life span ; ILS%) of mice pretreated with IL-2 and treated with hyperthermic chemotherapy compared with control: IL-2+ CIS (ILS%=260, 50) ; IL-2+ DOX + CIS (ILS%=200) ; IL-2 + MIT (ILS%=178, 05) ; IL-2 + CDL (ILS%=70, 20) ; IL-2+ DOX (ILS%=67, 92) ; IL-2 + 5-FU (ILS%=62, 69) ; IL-2+ 5-FU+ DOX (ILS%=55, 22). Treatment with IL-2+ 5-FU+ CIS was shown to be toxic to mice since all mice died before control group. Conclusion: The results suggest the synergistic effect of hyperthermia, chemotherapy and immunotherapy ; IL-2 significantly increases antitumor activity of hyperthermic chemotherapy and survival rate of mice with peritoneal carcinomatosis. It is likely that stimulative effect of IL-2 on hematopoiesis, differentiation and proliferation on stem cells as well as immunomodulation may be possible mechanism of protection of mice from development of peritoneal carcinomatosis.These treatments reduce side effect of chemotherapy treatment increasing life spin of mice.
Peritoneal carcinomatosis; hyperthermia; chemotherapy; immunotherapy; IL-2
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Podaci o prilogu
2007.
objavljeno
Podaci o matičnoj publikaciji
FIP 2007, Beijing China
Podaci o skupu
67th Interantional Congress of FIP, 2007, Beijing China
poster
31.08.2007-06.09.2007
Peking, Kina