Therapeutic Cell‐Cycle‐Decoy Efficacy of a Telomerase‐Dependent Adenovirus in an Orthotopic Model of Chemotherapy‐Resistant Human Stomach Carcinomatosis Peritonitis Visualized With FUCCI Imaging. Issue 11 (31st July 2017)

• Record Type: Journal Article
• Authors: Yano, Shuya; Takehara, Kiyoto; Tazawa, Hiroshi; Kishimoto, Hiroyuki; Urata, Yasuo; Kagawa, Shunsuke; Fujiwara, Toshiyoshi; Hoffman, Robert M.
• Is Part Of: Journal of cellular biochemistry. Volume 118:Issue 11(2017)
• Page Start: 3635
• Page End: 3642
• Publication Date: 2017-07-31
• Subjects: CARCINOMATOSIS PERITONITIS -- GASTRIC CANCER -- ORTHOTOPIC -- NUDE MICE -- TELOMERASE -- ADENOVIRUS -- FUCCI -- CELL CYCLE -- IMAGING -- CISPLATINUM -- PACLITAXEL; Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.25593
• Languages: English
• ISSNs: 0730-2312

Abstract

ABSTRACT: We have established an orthotopic nude‐mouse model of gastric cancer carcinomatosis peritonitis, a recalcitrant disease in human patients. Human MKN45 poorly‐differentiated human gastric cancer cells developed carcinomatosis peritonitis upon orthotopic transplantation in nude mice. The MKN45 cells expressed the fluorescent ubiquitination‐based cell cycle indicator (FUCCI) that color codes the phases of the cell cycle. The intra‐peritoneal tumors and ascites contained mostly quiescent G1 /Go cancer cells visualized as red by FUCCI imaging. Cisplatinum (CDDP) treatment did not reduce bloody ascites, and larger tumors formed in the peritoneal cavity after CDDP treatment in an early‐stage carcinomatosis peritonitis orthotopic mouse model. Paclitaxel‐treated mice had reduced ascites, but also had large tumor masses in the peritonium after treatment with cancer cells mostly in G0 /G1, visualized by FUCCI red. In contrast, OBP‐301 telomerase‐dependent adenovirus‐treated mice had no ascites and only small tumor nodules consisting of cancer cells mostly in S/G2 phases in the early‐stage carcinomatosis peritonitis model, visualized by FUCCI green. Furthermore, OBP‐301 significantly reduced the size of tumors ( P < 0.01) and ascites even in a late‐stage carcinomatosis peritonitis model. These results suggest that quiescent peritoneally‐disseminated gastric cancer cells are resistant to conventional chemotherapy, but OBP‐301 significantly reduced the weight of the tumors and increased survival, suggesting clinical potential. J. Cell. Biochem. 118: 3635–3642, 2017. © 2016 Wiley Periodicals, Inc. Abstract : Chemoresistance of stomach cancer carcinomatosis peritonitis is due in large part to the majority of the cells in the tumor being quiescent (upper three panels). The telomerase‐dependent adenovirus, OBP‐301, decoyed the quiescent cells within carcinomatosis peritonitis to begin to cycle and thereby rendering them chemosensitive (lower three panels). FUCCI imaging: red = G0 /G1 ‐ phase cells; green = S/G2‐ phase cells.