Shashni Babita, Ariyasu Shinya, Takeda Reisa, Suzuki Toshihiro, Shiina Shota, Akimoto Kazunori, Maeda Takuto, Aikawa Naoyuki, Abe Ryo, Osaki Tomohiro, Itoh Norihiko, Aoki Shin
Faculty of Pharmaceutical Sciences, Tokyo University of Science.
Center for Technologies Against Cancer, Tokyo University of Science.
Biol Pharm Bull. 2018 Apr 1;41(4):487-503. doi: 10.1248/bpb.b17-00776. Epub 2018 Jan 13.
Detection of anomalous cells such as cancer cells from normal blood cells has the potential to contribute greatly to cancer diagnosis and therapy. Conventional methods for the detection of cancer cells are usually tedious and cumbersome. Herein, we report on the use of a particle size analyzer for the convenient size-based differentiation of cancer cells from normal cells. Measurements made using a particle size analyzer revealed that size parameters for cancer cells are significantly greater (e.g., inner diameter and width) than the corresponding values for normal cells (white blood cells (WBC), lymphocytes and splenocytes), with no significant difference in shape parameters (e.g., circularity and convexity). The inner diameter of many cancer cell lines is greater than 10 µm, in contrast to normal cells. For the detection of WBC having similar size to that of cancer cells, we developed a PC software "Cancer Cell Finder" that differentiates them from cancer cells based on brightness stationary points on a cell surface. Furthermore, the aforementioned method was validated for cancer cell/clusters detection in spiked mouse blood samples (a B16 melanoma mouse xenograft model) and circulating tumor cell cluster-like particles in the cat and dog (diagnosed with cancer) blood samples. These results provide insights into the possible applicability of the use of a particle size analyzer in conjunction with PC software for the convenient detection of cancer cells in experimental and clinical samples for theranostics.
从正常血细胞中检测癌细胞等异常细胞对癌症诊断和治疗具有巨大潜在贡献。传统的癌细胞检测方法通常繁琐且麻烦。在此,我们报告使用粒度分析仪基于大小方便地区分癌细胞与正常细胞。使用粒度分析仪进行的测量显示,癌细胞的大小参数(例如内径和宽度)明显大于正常细胞(白细胞(WBC)、淋巴细胞和脾细胞)的相应值,而形状参数(例如圆形度和凸度)没有显著差异。与正常细胞相比,许多癌细胞系的内径大于10μm。为了检测与癌细胞大小相似的白细胞,我们开发了一款PC软件“癌细胞查找器”,它基于细胞表面的亮度固定点将它们与癌细胞区分开来。此外,上述方法在加标的小鼠血液样本(B16黑色素瘤小鼠异种移植模型)以及猫和狗(诊断为癌症)血液样本中的循环肿瘤细胞簇样颗粒的癌细胞/簇检测中得到了验证。这些结果为结合PC软件使用粒度分析仪在实验和临床样本中方便地检测癌细胞用于治疗诊断的可能适用性提供了见解。