Satoshi Murata1,2, Hiroshi Yamamoto1,3, Tomoharu Shimizu1, Hiroyuki Naitoh1,4, Tsuyoshi Yamaguchi1, Sachiko Kaida1, Katsushi Takebayashi1, Toru Miyake1, Tohru Tani1,5, Masaji Tani1. 1. Department of Surgery, Shiga University of Medical Science, Otsu, Shiga, Japan. 2. Cancer Center, Shiga University of Medical Science Hospital, Otsu, Shiga, Japan. 3. Department of Surgery, Kusatsu General Hospital, Kusatsu, Shiga, Japan. 4. Department of Surgery, Hino Memorial Hospital, Hino-cho, Gamou-gun, Shiga, Japan. 5. Biomedical Innovation Center, Shiga University of Medical Science, Otsu, Shiga, Japan.
Abstract
BACKGROUND AND OBJECTIVES: Optimized drug regimens for hyperthermic intraperitoneal chemotherapy (HIPEC) have not been standardized completely in patients with advanced gastric cancer (GC). We evaluated an optimized anti-tumor protocol comprising 5-fluorouracil (5-FU) combined with cisplatin (CDDP) and mitomycin C (MMC) in vitro for clinical use of HIPEC. METHODS: The sensitivities of 5-FU, CDDP, or MMC, alone or in combination, using different drug concentrations, exposure times, and hyperthermic conditions (42°C) were determined in vitro by the CD-DST method using 3 different differentiated GC cell lines. RESULTS: The tumor cell growth-inhibitory effect of 5-FU was concentration-dependent for all cell lines. In addition, 5-FU showed a hyperthermic sensitization effect at all drug concentrations for all cell lines. The appropriate concentration of each drug was 5-FU, 200 µg/mL; CDDP, 10 µg/mL; MMC, 2 µg/mL. Under hyperthermic conditions, most growth-inhibitory effects for each drug at 30 min was equivalent to 60 min of exposure; use of three drugs combined significantly inhibited growth compared with any of the drugs alone. CONCLUSION: An appropriate in vitro intraperitoneal chemotherapy regimen for GC was combined use of 5-FU, CDDP, and MMC at 42°C for 30 min.
BACKGROUND AND OBJECTIVES: Optimized drug regimens for hyperthermic intraperitoneal chemotherapy (HIPEC) have not been standardized completely in patients with advanced gastric cancer (GC). We evaluated an optimized anti-tumor protocol comprising 5-fluorouracil (5-FU) combined with cisplatin (CDDP) and mitomycin C (MMC) in vitro for clinical use of HIPEC. METHODS: The sensitivities of 5-FU, CDDP, or MMC, alone or in combination, using different drug concentrations, exposure times, and hyperthermic conditions (42°C) were determined in vitro by the CD-DST method using 3 different differentiated GC cell lines. RESULTS: The tumor cell growth-inhibitory effect of 5-FU was concentration-dependent for all cell lines. In addition, 5-FU showed a hyperthermic sensitization effect at all drug concentrations for all cell lines. The appropriate concentration of each drug was 5-FU, 200 µg/mL; CDDP, 10 µg/mL; MMC, 2 µg/mL. Under hyperthermic conditions, most growth-inhibitory effects for each drug at 30 min was equivalent to 60 min of exposure; use of three drugs combined significantly inhibited growth compared with any of the drugs alone. CONCLUSION: An appropriate in vitro intraperitoneal chemotherapy regimen for GC was combined use of 5-FU, CDDP, and MMC at 42°C for 30 min.
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Authors: Daan R Löke; Roxan F C P A Helderman; Jan Sijbrands; Hans M Rodermond; Pieter J Tanis; Nicolaas A P Franken; Arlene L Oei; H Petra Kok; Johannes Crezee Journal: Cancers (Basel) Date: 2020-11-26 Impact factor: 6.639
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