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研究方向
基于循环肿瘤细胞/肿瘤干细胞的癌症早期诊断和治疗

癌症是当前人类亟待解决的重大科学难题和社会问题。临床90%以上癌症病人死亡的原因是癌细胞的转移(Science 1559: 331, 2011)。其核心物质基础是循环肿瘤细胞(Circulating Tumor cells, CTC)及其集群(CTC cluster)的存在(Cell 176: 98, 2019)。因此,阻断、捕获和靶向CTC被认为是实现癌症早期诊断和转移后治疗的根本途径(Nature Reviews Clinical Oncology 16: 409, 2019)。

肿瘤的放射抗性和复发转移均与耐辐射肿瘤干细胞的存在密切相关。肿瘤干细胞(cancer stem-like cells, CSCs)是指肿瘤组织中一小部分具有自我更新能力和分化产生多种子代肿瘤细胞能力的细胞。2012年8月,肿瘤干细胞分别在体内皮肤癌、肠癌和脑癌中被追踪到(Nature 488: 522,2012;Science 337: 730, 2012)。同期Nature评论文章认为:这些研究证明肿瘤干细胞驱动了肿瘤的生长,为肿瘤干细胞在体内的存在提供了清晰直接的证据,表明治疗癌症可能需要彻底杀死这些细胞(Nature 488: 13, 2012)。单细胞测序研究发现,乳腺癌中CSC约占CTC的20.7%且起始了肿瘤的远端转移(Nature 526: 131, 2015)。


2010年本课题组开始专注耐受放化疗和高转移潜力的肿瘤(干)细胞研究。经过10年来的研究积累和广泛合作,课题组在CSC、CTC捕获/靶向等方向积累了较为独特的研究体系,与其他课题组和多家医院建立了合作,目前有4项临床合作研究,涉及癌症早筛诊断、治疗疗效监测和患者预后那个研究方向。


组内相关研究论文:

  1. Chunyang Lu§, Jian Xu§, Jintao Han, Xiao Li, Ningtao Xue, Jinsong Li, Wenhua Wu, Xinlei Sun, Yugang Wang, Qi Ouyang, Gen Yang*, Chunxiong Luo*.A novel microfluidic device integrating focus-separation speed reduction design and capture arrays for high-throughput capture of circulating tumor cells from whole blood. Lab on Chip. 2020 (In press)

  2. Quan, Qianghua; Wang, Xudong; Lu, Chunyang; Ma, Wenzong; Wang, Yugang; Xia, Guoliang; Wang, Chao*; Yang, Gen*. Cancer stem-like cells with hybrid epithelial/mesenchymal phenotype leading the collective invasion. Cancer Science 111: 467-476, 2020. (Cover Image)

  3. Jian Xu, Xudong Wang, Xiao Li, Gen Yang*, Chunxiong Luo*. High-throughput cell migration assay under combinatorial chemical environments by a novel 24-well-plate based device. Biomedical Microdevices 22: 40-47, 2020.

  4. Qianghua Quan, Xudong Wang, Chunyang Lu, Wenzong Ma, Jintao Han, Guoliang Xia, Gen Yang*, Chao Wang*, Association of extracellular matrix microarchitecture and three-dimensional collective invasion of cancer cells. Biotechnic & Histochemistry 95:(8): 605-612, 2020.

  5. Qibin Fu, Tuchen Huang, Xudong Wang, Chunyang Lu, Feng Liu, Gen Yang*, Yugang Wang, and Biao Wang*. Association of elevated reactive oxygen species and hyperthermia induced radiosensitivity in cancer stem-like cells. Oncotarget 8(60):101560-101571, 2017. 

  6. Qianghua Quan, Shuwen Zhang, Xudong Wang, Qi Ouyang, Yugang Wang, Gen Yang*, Chunxiong Luo*. A parallel and quantitative cell migration assay using a novel multi-well-based device. Biomed Microdevices 18(6): 1-8; 2016.

  7. Yu Liu, Alisa Kobayashi, Qibin Fu, Gen Yang*, Teruaki Konishi*, Yukio Uchihori, Tom K. Hei, Yugang Wang. Rescue of Targeted Non stem-Like Cells from Bystander Stem-Like Cells in Human Fibrosarcoma HT1080. Radiation Research 184, 334-340; 2015.

  8. Ying Liang, Qibin Fu, Weikang Wang, Yu Liu, Feng Liu, Gen Yang*, Yugang Wang. An integrated on-line irradiation and in situ live cell imaging system. Nuclear Instruments and Methods in Physics Research B, 358: 26-31; 2015. 

  9. Yu Liu, Alisa Kobayashi, Takeshi Maeda, Qibin Fu, Masakazu Oikawa, Gen Yang*, Teruaki Konishi*, Yukio Uchihori, Tom K. Hei, Yugang Wang. Target irradiation induced bystander effects between stem-like and non stem-like cancer cells. Mutation Research, 773: 43-47; 2015. 

  10. Weikang Wang, Yi Quan, Qibin Fu, Yu Liu, Ying Liang, Jingwen Wu, Gen Yang*, Chunxiong Luo, Qi Ouyang, and Yugang Wang. Dynamics between cancer cell subpopulations reveals a model coordinating with both hierarchical and stochastic concepts. PLOS One, 9(1): e84654; 2014. 

  11. Yi Quan†, Ying Yan†, Xiaoli Wang, Qibin Fu, Weikang Wang, Jingwen Wu, Gen Yang*, Jun Ren*, and Yugang Wang. Impact of cell dissociation on identification of breast cancer stem cells, Cancer Biomarkers, 12: 125-133; 2013. 

  12. Qibin Fu, Yi Quan, Weikang Wang, Tao Mei, Jingwen Wu, Jia Li, Gen Yang*, Xiaotang Ren, Jianming Xue, Yugang Wang, Response of cancer stem-like cells and non-stem cancer cells to proton and γ-ray irradiation. Nuclear Instruments and Methods in Physics Research B; 286: 346-50; 2012.

  13. Yi Quan, Qibin Fu, Tao Mei, Jingwen Wu, Jia Li, Gen Yang*, Yugang Wang, Accumulation efficiency of cancer stem-like cells post γ-ray and proton irradiation. Nuclear Instruments and Methods in Physics Research B; 286: 341-5; 2012.

  14.  Gen Yang, Yi Quan, Weikang Wang, Qibin Fu, Jingwen Wu, Tao Mei, Jia Li, Yubo Tang, Chunxiong Luo, Qi Ouyang, Shaopeng Chen, Lijun Wu, Tom K. Hei, and Yugang Wang, Dynamic equilibrium between cancer stem cells and non-stem cancer cells in human SW620 and MCF-7 cancer cell populations. British Journal of Cancer; 106: 1512-9; 2012.

  15. Jingwen Wu, Qibin Fu, Yi Quan, Weikang Wang, Tao Mei, Jia Li, Gen Yang*, Xiaotang Ren, Jianming Xue, Yugang Wang, Repair rates of DNA double-strand breaks under low doses of proton and γ-ray irradiation. Nuclear Instruments and Methods in Physics Research B; 276:1-6; 2012.