Automated Assessment of Cancer Drug Efficacy On Breast Tumor Spheroids in Aggrewell™400 Plates Using Image Cytometry

Author(s):  
Shilpaa Mukundan ◽  
Jordan Bell ◽  
Matthew Teryek ◽  
Charles Hernandez ◽  
Andrea C. Love ◽  
...  
Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3355 ◽  
Author(s):  
Wanyoung Lim ◽  
Sungsu Park

Three-dimensional (3D) cell culture is considered more clinically relevant in mimicking the structural and physiological conditions of tumors in vivo compared to two-dimensional cell cultures. In recent years, high-throughput screening (HTS) in 3D cell arrays has been extensively used for drug discovery because of its usability and applicability. Herein, we developed a microfluidic spheroid culture device (μFSCD) with a concentration gradient generator (CGG) that enabled cells to form spheroids and grow in the presence of cancer drug gradients. The device is composed of concave microwells with several serpentine micro-channels which generate a concentration gradient. Once the colon cancer cells (HCT116) formed a single spheroid (approximately 120 μm in diameter) in each microwell, spheroids were perfused in the presence of the cancer drug gradient irinotecan for three days. The number of spheroids, roundness, and cell viability, were inversely proportional to the drug concentration. These results suggest that the μFSCD with a CGG has the potential to become an HTS platform for screening the efficacy of cancer drugs.


2020 ◽  
Vol 3 (9) ◽  
pp. 6273-6283
Author(s):  
Zhuhao Wu ◽  
Zhiyi Gong ◽  
Zheng Ao ◽  
Junhua Xu ◽  
Hongwei Cai ◽  
...  
Keyword(s):  

Author(s):  
Haley Brooke Johnson ◽  
Emily E. Fannin ◽  
Alexandra Thomas ◽  
Jared A Weis

Author(s):  
Wanyoung Lim ◽  
Sungsu Park

Three-dimensional (3D) cell culture is considered more clinically relevant in mimicking the structural and physiological conditions of tumors in vivo compared to two-dimensional cell cultures. In recent years, high-throughput screening (HTS) in 3D cell arrays has been extensively used for drug discovery because of its usability and applicability. Herein, we developed a microfluidic spheroid culture device (μFSCD) with a concentration gradient generator (CGG) that enabled cells to form spheroids and grow in the presence of cancer drug gradients. The device is composed of concave microwells with several serpentine micro-channels which generate a concentration gradient. Once the colon cancer cells (HCT116) formed a single spheroid (approximately 120 μm in diameter) in each microwell, spheroids were perfused in the presence of the cancer drug gradient irinotecan for 3 days. The number of spheroids, roundness, and cell viability, were inversely proportional to the drug concentration. These results suggest that the μFSCD with a CGG has the potential to become an HTS platform for screening the efficacy of cancer drugs.


2019 ◽  
Vol Volume 12 ◽  
pp. 11153-11173
Author(s):  
Regina-Veronicka Kalaydina ◽  
Hedi Zhou ◽  
Elena Markvicheva ◽  
Sergey Burov ◽  
Farhana Zulkernine ◽  
...  

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
JungHo Kong ◽  
Heetak Lee ◽  
Donghyo Kim ◽  
Seong Kyu Han ◽  
Doyeon Ha ◽  
...  

Abstract Cancer patient classification using predictive biomarkers for anti-cancer drug responses is essential for improving therapeutic outcomes. However, current machine-learning-based predictions of drug response often fail to identify robust translational biomarkers from preclinical models. Here, we present a machine-learning framework to identify robust drug biomarkers by taking advantage of network-based analyses using pharmacogenomic data derived from three-dimensional organoid culture models. The biomarkers identified by our approach accurately predict the drug responses of 114 colorectal cancer patients treated with 5-fluorouracil and 77 bladder cancer patients treated with cisplatin. We further confirm our biomarkers using external transcriptomic datasets of drug-sensitive and -resistant isogenic cancer cell lines. Finally, concordance analysis between the transcriptomic biomarkers and independent somatic mutation-based biomarkers further validate our method. This work presents a method to predict cancer patient drug responses using pharmacogenomic data derived from organoid models by combining the application of gene modules and network-based approaches.


2020 ◽  
Author(s):  
Yunfeng Li ◽  
Nancy Khuu ◽  
Elisabeth Prince ◽  
Huachen Tao ◽  
Ningtong Zhang ◽  
...  

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