García-Santos Esther Pilar, Padilla-Valverde David, Villarejo-Campos Pedro, Murillo-Lázaro Cristina, Fernández-Grande Esther, Palomino-Muñoz Teodoro, Rodríguez-Martínez Marta, Amo-Salas Mariano, Nuñez-Guerrero Paloma, Sánchez-García Susana, Puerto-Puerto Alejandro, Martín-Fernández Jesús
Servicio de Cirugía General y de Aparato Digestivo, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain.
Servicio de Cirugía General y de Aparato Digestivo, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain.
Pancreatology. 2016 Jul-Aug;16(4):632-9. doi: 10.1016/j.pan.2016.04.031. Epub 2016 May 12.
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.
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.
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).
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.
胰腺癌的起源已被确定为一群具有CD133 + CXCR4 +免疫表型的恶性胰腺干细胞。这些细胞具有早期局部区域侵袭的高能力，是胰腺癌早期复发和高死亡率的原因。我们提出一项研究，通过减少胰腺癌干细胞CD133 + CXCR4 +的体积和肿瘤亚群来降低胰腺癌的肿瘤进展。因此，我们开发了一种新的治疗模型，其特征是应用吉西他滨进行热灌注化疗（HIPEC）。
胰腺肿瘤细胞系：人细胞系BxPC - 3。动物模型涉及18只体重150 - 200克的5周龄免疫抑制大鼠。根据腹膜癌指数（PCI），将13×10(6)个细胞/毫升均匀分布植入13个腹盆腔象限，并随机分为三个治疗组。第一组（4只大鼠）接受静脉注射生理盐水。第二组（6只大鼠）接受静脉注射吉西他滨。第三组（8只大鼠）接受41℃下30分钟的热灌注化疗，同时联合吉西他滨静脉注射。组织学研究证实为胰腺癌，并对胰腺癌干细胞CD133 + CXCR4 +肿瘤细胞进行免疫组化定量分析。
与其他两组相比，热灌注化疗组中胰腺癌干细胞CD133 + CXCR4 +的数量下降（p < 0.001）。治疗组之间的PCI有所下降（p < 0.05）。
初步结果令人鼓舞，因为与其他两个治疗组相比，热灌注化疗组中癌症干细胞CD133 + CXCR4 +的数量减少，肿瘤体积减小。所有结论仅对BxPC3细胞系有效，热灌注化疗对Kras驱动的胰腺肿瘤的影响仍有待确定。
