Institute of Anatomy, University of Leipzig, Leipzig, Germany; University Cancer Center Leipzig, University Hospital Leipzig, Leipzig, Germany.
Institute of Anatomy, University of Leipzig, Leipzig, Germany; University Cancer Center Leipzig, University Hospital Leipzig, Leipzig, Germany.
Clin Colorectal Cancer. 2018 Jun;17(2):e189-e199. doi: 10.1016/j.clcc.2017.11.002. Epub 2017 Nov 21.
Nonresponse to chemotherapy in colorectal carcinoma (CRC) is still a clinical problem. For most established treatment regimens, no predictive biomarkers are available. Patient-derived tumor slice culture may be a promising ex vivo technology to assess the drug susceptibility in individual tumors.
Patient-derived slice cultures of CRC specimens were prepared according to a standardized protocol and treated with different concentrations of 5-fluorouracil (5-FU) and an adapted FOLFOX regimen (5-FU and oxaliplatin) to investigate histologic response. Additionally, a semi-automatized readout using fluorescent stain-specific segmentation algorithms for Image J was established to quantify changes in tumor proliferation. Nonresponse to chemotherapy was defined as persisting tumor cell proliferation.
Slices treated with 5-FU showed lower tumor cell fractions and dose-dependent alterations of proliferating tumor cells compared with controls (1 μM, Δ +3%; 10 μM, Δ -9%; 100 μM, Δ -15%). Individual tumor samples were examined and differences in chemotherapy susceptibility could be observed. Untreated slice cultures contained an average tumor cell fraction of 31% ± 7%. For all samples, the histopathologic characteristics exhibited some degree of intratumoral heterogeneity with regard to tumor cell morphology and distribution. The original tumor matched the features found in slices at baseline and after 3 days of cultivation.
Patient-derived slice cultures may help to predict response to clinical treatment in individual patients with CRC. Future studies need to address the problem of tumor heterogeneity and evolution. Prospective correlation of ex vivo results with the clinical course of treated patients is warranted.
结直肠癌（CRC）对化疗无反应仍然是一个临床问题。对于大多数既定的治疗方案，尚无预测性生物标志物。患者来源的肿瘤切片培养可能是一种很有前途的体外技术，可以评估个体肿瘤的药物敏感性。
根据标准化方案制备 CRC 标本的患者来源的切片培养物，并以不同浓度的 5-氟尿嘧啶（5-FU）和改良的 FOLFOX 方案（5-FU 和奥沙利铂）进行处理，以研究组织学反应。此外，还建立了使用荧光染色特异性分割算法的半自动读数方法，用于量化肿瘤增殖的变化。对化疗无反应的定义为肿瘤细胞持续增殖。
与对照组相比，用 5-FU 处理的切片显示出较低的肿瘤细胞分数和增殖肿瘤细胞的剂量依赖性改变（1 μM，Δ +3%；10 μM，Δ -9%；100 μM，Δ -15%）。个别肿瘤样本进行了检查，观察到化疗敏感性的差异。未经处理的切片培养物中平均含有 31%±7%的肿瘤细胞分数。对于所有样本，组织病理学特征在肿瘤细胞形态和分布方面表现出一定程度的肿瘤内异质性。原始肿瘤与基线和培养 3 天后切片中发现的特征相匹配。
患者来源的切片培养物可能有助于预测 CRC 患者个体对临床治疗的反应。未来的研究需要解决肿瘤异质性和进化的问题。有必要对体外结果与接受治疗患者的临床病程进行前瞻性相关性分析。
