KMID : 1011820230640030296
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Investigative and Clinical Urology 2023 Volume.64 No. 3 p.296 ~ p.305
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Efficacy of recombinant Bacillus Calmette-Guerin containing dltA in in vivo three-dimensional bio-printed bladder cancer-on-a-chip and ex vivo orthotopic mouse model
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Choi Joong-Won
Jung Tae-Young Kim Jung-Hoon Maeng Se-Jung Kang Su-Jeong Kim Mirinae Choi Young-Wook Choi Se-Young Kim Sung-Hwan Chang In-Ho
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Abstract
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Purpose : We investigated the efficacy and optimal dosage of recombinant Bacillus Calmette-Guerin-dltA (rBCG-dltA) in a high-throughput 3D bio-printed bladder cancer-on-a-chip (BCOC) and orthotopic bladder cancer mouse model.
Materials and Methods : We fabricated high-throughput BCOC with microfluidic systems, enabling efficient drug screening. The efficacy of rBCG-dltA was evaluated using BCOC by the cell viability assay, monocyte migration assay, and measuring cytokine levels. The anti-tumor effect was compared using the orthotopic bladder cancer mouse model.
Results : The cell proliferation rates of T24 and 253J bladder cancer cell lines (mean¡¾standard error) were measured at three days after treatment. In T24 cell line, there was significantly decreased T24 cells compared to control at rBCG 1 multiplicity of infection (MOI) and 10 MOI (30 MOI: 63.1¡¾6.4, 10 MOI: 47.4¡¾5.2, 1 MOI: 50.5¡¾7.5, control: 100.0¡¾14.5, p<0.05). In 253J cell line, a statistically significant decrease in 253J cell count compared to control and mock BCG 30 MOI (30 MOI: 11.2¡¾1.3, 10 MOI: 22.5¡¾2.3, 1 MOI: 39.4¡¾4.7, Mock: 54.9¡¾10.8, control: 100.0¡¾5.6, p<0.05). The migration rates of THP-1 cells showed increased patterns after rBCG-dltA treatment in BCOC. The concentration of tumor necrosis factor-¥á and interleukin-6 after rBCG-dltA 30 MOI treatment was higher than control in T24 and 253J cell line.
Conclusions : In conclusion, rBCG-dltA has the potential to have better anti-tumor activity and immunomodulatory effects than BCG. Furthermore, high-throughput BCOCs have potential to reflect the bladder cancer microenvironment.
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KEYWORD
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Bioprinting, Mycobacterium bovis, Tumor microenvironment
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