PT  - JOURNAL ARTICLE
AU  - KUNIO TAKIGUCHI
AU  - TAKERU NAKAMOTO
AU  - HIROYUKI INAGAWA
AU  - CHIE KOHCHI
AU  - TAKASHI NISHIZAWA
AU  - NAOFUMI NAGASUE
AU  - GEN-ICHIRO SOMA
TI  - Profile of Cytokines Produced in Tumor Tissue after Administration of Cyclophosphamide in a Combination Therapy with Tumor Necrosis Factor
DP  - 2004 May 01
TA  - Anticancer Research
PG  - 1823--1828
VI  - 24
IP  - 3A
4099  - http://ar.iiarjournals.org/content/24/3A/1823.short
4100  - http://ar.iiarjournals.org/content/24/3A/1823.full
SO  - Anticancer Res2004 May 01; 24
AB  - Background: Recent studies have shown that locoregional administration of tumor necrosis factor (TNF) or production of endogenous TNF in tumor tissue with a chemotherapeutic agent showed considerable antitumor effect without severe toxicities. To analyze the immunological role of chemotherapeutic agents in locoregional TNF therapy, the effect of cyclophosphamide (CY) on cytokine production after ONO-4007 treatment was examined. Materials and Methods: Seven days after inoculation of Meth A fibrosarcoma in BALB/c mice, CY (100-150 mg/kg) was injected intraperitoneally and, after another 7 days, ONO-4007 (30mg/kg) was injected intravenously. A competitive PCR quantitative analysis of the induced cytokine messenger RNA (mRNA) was performed for IL-12 (p40), TGF-β, TNF-α, IL-1β, IL-10 and IL-6. Results: The antitumor effect of ONO-4007 was enhanced by preadministration of CY. CY significantly enhanced IL-12 (p40) mRNA compared to that by ONO-4007 alone. No increase in TGF-β mRNA was observed in either treatment. Conclusion: The preadministration of CY enhances IL-12 production in tumor tissues and shifts the cytokine profile to the dominant Th1 type. Copyright© 2004 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved