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.
OBJECTIVE
The 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.


METHODS
Pancreatic 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 × 10(6) 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.


RESULTS
There 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).


CONCLUSIONS
The 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.
Servicio de Cirugía General y de Aparato Digestivo, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain. Electronic address: esther_garcia_santos@hotmail.com.
Esther Pilar
EP
García-Santos
Servicio de Cirugía General y de Aparato Digestivo, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain.
David
D
Padilla-Valverde
Servicio de Cirugía General y de Aparato Digestivo, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain.
Pedro
P
Villarejo-Campos
Servicio de Anatomía Patológica, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain.
Cristina
C
Murillo-Lázaro
Servicio de Análisis Clínicos, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain.
Esther
E
Fernández-Grande
Servicio de Análisis Clínicos, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain.
Teodoro
T
Palomino-Muñoz
Servicio de Farmacia, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain.
Marta
M
Rodríguez-Martínez
Facultad de Medicina de Ciudad Real, Universidad de Castilla La Mancha, Spain.
Mariano
M
Amo-Salas
Servicio de Cirugía General y de Aparato Digestivo, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain.
Paloma
P
Nuñez-Guerrero
Servicio de Cirugía General y de Aparato Digestivo, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain.
Susana
S
Sánchez-García
Servicio de Urología, Hospital General La Mancha Centro, Alcázar de San Juan, Ciudad Real, Spain.
Alejandro
A
Puerto-Puerto
Servicio de Cirugía General y de Aparato Digestivo, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain.
Jesús
J
Martín-Fernández
D000071916:AC133 Antigen / Q000276:immunology*; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy*; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018450:Disease Progression; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods*; D007274:Injections, Intraperitoneal; D008297:Male; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010534:Peritoneal Neoplasms / Q000188:drug therapy*; D051381:Rats; D011923:Rats, Nude; D019718:Receptors, CXCR4 / Q000276:immunology*; D000093542:Gemcitabine
D000071916:AC133 Antigen; D000964:Antimetabolites, Antineoplastic; C527276:CXCR4 protein, human; D019718:Receptors, CXCR4; D003841:Deoxycytidine; D000093542:Gemcitabine
Cancer stem cells; Gemcitabine; Hyperthermic intra-abdominal chemotherapy; Pancreatic cancer; Pancreatic cancer stem cells; Peritoneal carcinomatosis