Katuwal Binit, Aleissa Maryam, Varshney Neha, Jacobs Michael J, Mittal Vijay, Bhullar Jasneet
Ascension Providence Hospital-Michigan State University/College of Human Medicine, Southfield, MI. (Dr. Katuwal).
Fellow of Colorectal Surgery, Ascension Providence Hospital-Michigan State University/College of Human Medicine, Southfield, MI. (Dr. Aleissa).
JSLS. 2024 Oct-Dec;28(4). doi: 10.4293/JSLS.2024.00048. Epub 2025 Jan 17.
Orthotopic murine models of pancreatic cancer represent an important tool for evaluating treatment strategies. Several genetically modified mouse tumors and xenograft models have been reported. Genetic models have unpredictable growth and variable waiting period, while orthotopic models are operative ones, difficult to create and result in irregular metastasis. There is a constant endeavor to create an orthotopic model which replicates the human disease process.
Orthotopic human pancreatic tumors were induced in 20 SCID mice using a novel technique. Low dose electrocoagulation of pancreas under laparoscopic guidance (using Coloview-mouse colonoscope) with thin electrode, followed by injection of 0.1 cc BxPC3 pancreatic cancer cells was done (n = 12, study group). Control mice underwent electrocoagulation alone (n = 4, group 1) and tumor cell injection alone (n = 4, group 2). Mice were evaluated for tumor growth and metastasis by necropsy (4 and 8 weeks for experimental group; 8 weeks for control group).
Tumors were detected in 11/12 mice in experimental group, 1/4 in control group 2, and none in control group 1. Over time there was an increase in tumor growth, tumor volume, lymphovascular invasion of pancreas, with metastasis to lymph nodes and surrounding organs.
We report a novel concept of tumor cell implantation at site of electrocoagulation of pancreas. Combined with the minimally invasive technique, yields a replicative orthotopic murine model of pancreatic cancer. Our model is minimally invasive, easy to create, and overcomes the limitations of the existing models while questions the possibility free floating tumor cell implantation at resection site.
胰腺癌原位小鼠模型是评估治疗策略的重要工具。已报道了几种基因改造小鼠肿瘤和异种移植模型。基因模型生长不可预测且等待期可变,而原位模型是手术模型,难以创建且会导致不规则转移。人们一直在努力创建一种能复制人类疾病过程的原位模型。
采用新技术在20只SCID小鼠中诱导出原位人胰腺肿瘤。在腹腔镜引导下(使用Coloview小鼠结肠镜)用细电极对胰腺进行低剂量电凝,然后注射0.1 cc BxPC3胰腺癌细胞(n = 12,研究组)。对照小鼠分别仅接受电凝(n = 4,第1组)和仅接受肿瘤细胞注射(n = 4,第2组)。通过尸检评估小鼠的肿瘤生长和转移情况(实验组为4周和8周;对照组为8周)。
实验组12只小鼠中有11只检测到肿瘤,第2组对照组4只中有1只检测到肿瘤,第1组对照组未检测到肿瘤。随着时间推移,肿瘤生长、肿瘤体积、胰腺的淋巴管浸润增加,并出现向淋巴结和周围器官的转移。
我们报道了一种在胰腺电凝部位植入肿瘤细胞的新概念。结合微创技术,产生了一种可复制的胰腺癌原位小鼠模型。我们的模型微创、易于创建,克服了现有模型的局限性,同时对在切除部位自由漂浮肿瘤细胞植入的可能性提出了质疑。