Immunotherapy in liver tumors: III. A new experimental model of metastatic liver tumors from colorectal carcinoma for cytokine therapy.
A new model of metastatic liver tumors in Wistar/Furth rats is introduced. A colorectal adenocarcinoma cell line (LDLX40) induced by 1,2-dimethylhydrazine was injected through one of the branches of the ileal mesenteric vein to develop metastatic liver tumors in rats. On day 30 after the inoculation of tumor cells, micrometastases were detected under microscopy in all animals that received tumor inoculation. Macrometastases in 87.7% of animals were found by either the tumor staining test or ultrasonography. No extrahepatic tumor developed in this tumor model. To observe the effects of different treatment strategies on metastatic liver tumors, 35 animals were randomly divided into four groups. Group I served as control. Group II underwent hepatic artery ligation (HAL). Group III received intraportal administration of recombinant interleukin-2 (rIL-2) and interferon-alpha (IFN-alpha). Group IV had intraportal medication of rIL-2 and IFN-alpha + HAL (the IIH protocol). Results indicated that rapid tumor growth was seen in the control tumors. HAL produced little response to metastatic liver tumors as compared to the control group (P > 0.05). The combined application of rIL-2 and IFN-alpha showed an improved result, with 22% of tumor growth inhibition or regression (P < 0.05 compared to the control group). Twenty-eight percent of tumor growth restraint or regression was found in the group treated with the IIH protocol (P < 0.05 compared to the control group). We conclude that this new experimental model of metastatic liver tumors is reproducible, and that the IIH protocol is effective in the treatment of metastatic liver tumors in rats. These beneficial effects from the IIH protocol may be introduced into patients with metastatic liver tumors.
Liu
D L
DL
Department of Surgery and Oncology, Lund University, Sweden.
Radnell
M
M
Svanberg
K
K
Seifert
J
J
D000230:Adenocarcinoma / Q000473:pathology*; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000473:pathology*; D004195:Disease Models, Animal; D006499:Hepatic Artery / Q000601:surgery; D007082:Ileum / Q000098:blood supply; D007167:Immunotherapy; D007269:Injections, Intra-Arterial; D016898:Interferon-alpha / Q000008:administration & dosage / Q000494:pharmacology*; D007376:Interleukin-2 / Q000008:administration & dosage / Q000494:pharmacology*; D008026:Ligation; D008114:Liver Neoplasms, Experimental / Q000473:pathology / Q000556:secondary* / Q000628:therapy*; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects / Q000276:immunology; D009368:Neoplasm Transplantation; D051381:Rats; D011920:Rats, Inbred WF; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
D016898:Interferon-alpha; D007376:Interleukin-2; D011994:Recombinant Proteins