scholarly journals Microfluidic Device for Screening for Target Cell-Specific Binding Molecules by Using Adherent Cells

Micromachines ◽  
2019 ◽  
Vol 10 (1) ◽  
pp. 41 ◽  
Author(s):  
Maho Kaminaga ◽  
Tadashi Ishida ◽  
Tetsuya Kadonosono ◽  
Shinae Kizaka-Kondoh ◽  
Toru Omata

This paper proposes a microfluidic device for screening molecules such as aptamers, antibodies, proteins, etc. for target cell-specific binding molecules. The discovery of cancer cell-specific binding molecules was the goal of this study. Its functions include filtering non-target cell-binding molecules, trapping molecules on the surface of target cells, washing away unbound molecules, and collecting target cell-specific binding molecules from target cells. These functions were effectively implemented by using our previously developed micro pillar arrays for cell homogeneous dispersion and pneumatic microvalves for tall microchannels. The device was also equipped with serially connected filter chambers in which non-target cells were cultured to reduce the molecules binding to non-target cells as much as possible. We evaluated the performance of the device using cancer cell lines (N87 cells as target cells and HeLa cells as non-target cells) and two fluorescent dye-labeled antibodies: Anti-human epidermal growth factor receptor 2 (anti-HER2) antibody that binds to target cells and anti-integrin antibody that binds to non-target cells. The results showed that the device could reduce anti-integrin antibodies to the detection limit of fluorescent measurement and collect anti-HER2 antibodies from the target cells.

PLoS ONE ◽  
2018 ◽  
Vol 13 (2) ◽  
pp. e0192927
Author(s):  
Alexey V. Danilov ◽  
Divas Neupane ◽  
Archana Sidalaghatta Nagaraja ◽  
Elena V. Feofanova ◽  
Leigh Ann Humphries ◽  
...  

2006 ◽  
Vol 13 (4) ◽  
pp. 1173-1183 ◽  
Author(s):  
Michael W Yeh ◽  
Jean-Philippe Rougier ◽  
Jin-Woo Park ◽  
Quan-Yang Duh ◽  
Mariwil Wong ◽  
...  

Mechanisms of invasion in thyroid cancer remain poorly understood. We hypothesized that signaling via the epidermal growth factor receptor (EGFR) stimulates thyroid cancer cell invasion by altering the expression and cleavage of matrix metalloproteinases (MMPs). Papillary and follicular carcinoma cell lines were treated with EGF, the EGFR tyrosine kinase inhibitor AG1478, and the MMP inhibitors GM-6001 and Col-3. Flow cytometry was used to detect EGFR. In vitro invasion assays, gelatin zymography, and quantitative reverse transcription-PCR were used to assess the changes in invasive behavior and MMP expression and activation. All cell lines were found to overexpress functional EGFR. EGF stimulated invasion by thyroid cancer cells up to sevenfold (P < 0.0001), a process that was antagonized completely by AG1478 and Col-3, partially by GM-6001, but not by the serine protease inhibitor aprotinin. EGF upregulated expression of MMP-9 (2.64- to 8.89-fold, P < 0.0001) and membrane type-1 MMP (MT1-MMP, 1.97- to 2.67-fold, P < 0.0001). This effect was blocked completely by AG1478 and partially by Col-3. The activation of MMP-2 paralleled MT1-MMP expression. We demonstrate that MMPs are critical effectors of invasion in the papillary and follicular thyroid cancer cell lines studied. Invasion is regulated by signaling through EGFR, an effect mediated by augmentation of gelatinase expression and activation. MMP inhibitors and growth factor antagonists may be effective tumoristatic agents for the treatment of aggressive thyroid carcinomas.


2020 ◽  
Vol 40 (10) ◽  
pp. 2455-2468 ◽  
Author(s):  
Mohammed S. Al Suraih ◽  
Christy E. Trussoni ◽  
Patrick L. Splinter ◽  
Nicholas F. LaRusso ◽  
Steven P. O’Hara

PLoS ONE ◽  
2011 ◽  
Vol 6 (10) ◽  
pp. e26815 ◽  
Author(s):  
Alexey V. Danilov ◽  
Divas Neupane ◽  
Archana Sidalaghatta Nagaraja ◽  
Elena V. Feofanova ◽  
Leigh Ann Humphries ◽  
...  

2012 ◽  
Vol 30 (13) ◽  
pp. 1505-1512 ◽  
Author(s):  
Andrew J. Weickhardt ◽  
Tim J. Price ◽  
Geoff Chong ◽  
Val Gebski ◽  
Nick Pavlakis ◽  
...  

Purpose This preclinical and phase II study evaluated the efficacy and safety of the combination of cetuximab and erlotinib in metastatic colorectal cancer (mCRC). Patients and Methods The activity and mechanism of action of the combination of cetuximab plus erlotinib were investigated in vitro in colorectal cancer cell lines. In the clinical study, patients with chemotherapy-refractory mCRC were treated with cetuximab 400 mg/m2 as a loading dose and then weekly cetuximab 250 mg/m2 with erlotinib 100 mg orally daily. The primary end point was response rate (RR), which was evaluated separately in KRAS wild-type (WT) versus KRAS mutant tumors. Secondary end points included toxicity, progression-free survival (PFS), and overall survival. Target accrual was 50 patients, with a one-stage design. Results Preclinical studies demonstrated synergistic activity of cetuximab and erlotinib cotreatment on growth inhibition of colon cancer cell lines both as a result of enhanced inhibition of the epidermal growth factor receptor pathway and differential effects on STAT3. In the clinical study, 50 patients were enrolled, with 48 patients evaluable for response. The overall RR was 31% (95% CI, 26% to 57%), with a median PFS of 4.6 months (95% CI, 2.8 to 5.6 months). RR was 41% (95% CI, 26% to 57%) in KRAS WT tumors, with a median PFS of 5.6 months (95% CI, 2.9 to 5.6 months). There was no response in 11 patients with KRAS mutations. Frequent grade 3 and 4 toxicities were rash (48%), hypomagnesaemia (18%), and fatigue (10%). Conclusion The combination of cetuximab and erlotinib synergistically inhibits growth of colon cancer cell lines, achieves promising efficacy in patients with KRAS WT mCRC, and merits evaluation in further randomized studies.


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