The utility of hyperthermic intra-abdominal chemotherapy with gemcitabine for the inhibition of tumor progression in an experimental model of pancreatic peritoneal carcinomatosis,in relation to their behavior with pancreatic cancer stem cells CD133+ CXCR4+ |
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| Affiliation: | 1. Diagnostic Molecular Pathology Laboratory, Anatomic Pathology Department, A.C. Camargo Cancer Center, Brazil;2. Laboratory of Investigative Pathology, CIPE/A.C. Camargo Cancer Center, Brazil;3. Surgical Oncology Department, A.C. Camargo Cancer Center, Brazil;4. Abdominal Surgery Department, A.C. Camargo Cancer Center, Brazil;5. Laboratory of Genomics and Molecular Biology, CIPE/ A.C. Camargo Cancer Center, Brazil |
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| Abstract: | ObjectiveThe origin of pancreatic cancer has been identified as a population of malignant pancreatic stem cells CD133+ CXCR4+ immunophenotype. These cells have high capacity for early locoregional invasion, being responsible for early recurrence and high mortality rates of pancreatic cancer. We propose a study for decreasing tumor progression of pancreatic cancer by reducing the volume and neoplastic subpopulation of pancreatic cancer stem cells CD133+ CXCR4+. Therefore, we develop a new therapeutic model, characterized by the application of HIPEC (Hyperthermic Intraperitoneal Chemotherapy) with gemcitabine.DesignPancreatic tumor cell line: human cell line BxPC-3. The animal model involved 18 immunosuppressed rats 5 weeks weighing 150–200 gr. The implantation of 13 × 106 cells/mL was performed with homogeneous distribution in the 13 abdominopelvic quadrants according to the peritoneal carcinomatosis index (PCI) and were randomized into three treatment groups. Group I (4 rats) received intravenous saline. Group II (6 rats) received intravenous gemcitabine. Group III (8 rats) received HIPEC at 41 °C for 30 min with gemcitabine + gemcitabine IV. A histological study confirmed pancreatic cancer and immunohistochemical quantification of pancreatic cancer stem cells CD133+ CXCR4+ tumor cells.ResultsThere was a population decline of pancreatic cancer stem cells CD133+ CXCR4+ in the HIPEC group with respect to the other two groups (p < 0.001). There was a decrease in PCI between treatment groups (p < 0.05).ConclusionThe initial results are encouraging since there is a declining population of cancer stem cells CD133+ CXCR4+ in the HIPEC group and decreased tumor volume compared to the other two treatment groups. All the conclusions are only valid for BxPC3 cell line, and the effects HIPEC on Kras-driven pancreatic tumors remain to be determined. |
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| Keywords: | Pancreatic cancer Hyperthermic intra-abdominal chemotherapy Peritoneal carcinomatosis Gemcitabine Cancer stem cells Pancreatic cancer stem cells |
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