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
| Autor: | Hiroshi Tazawa, Yasuo Urata, Toshiyoshi Fujiwara, Robert M. Hoffman, Shunsuke Kagawa, Hiroyuki Kishimoto, Shuya Yano, Kiyoto Takehara |
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| Rok vydání: | 2017 |
| Předmět: |
G2 Phase
0301 basic medicine Telomerase Mice Nude Peritonitis Adenocarcinoma Biochemistry Adenoviridae S Phase 03 medical and health sciences Peritoneal cavity Stomach Neoplasms Ascites medicine Animals Humans Molecular Biology Peritoneal Neoplasms business.industry Cancer Neoplasms Experimental Cell Biology Cell cycle medicine.disease Virology Neoplasm Proteins 030104 developmental biology medicine.anatomical_structure Cancer cell Cancer research medicine.symptom business |
| Zdroj: | Journal of Cellular Biochemistry. 118:3635-3642 |
| ISSN: | 1097-4644 0730-2312 |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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