Assessing Drug Efficacy in a Miniaturized Pancreatic Cancer In Vitro 3D Cell Culture Model

2016 ◽  
Vol 14 (7) ◽  
pp. 367-380 ◽  
Author(s):  
Todd B. Shelper ◽  
Carrie J. Lovitt ◽  
Vicky M. Avery
2021 ◽  
Author(s):  
Sajjad Sharifi ◽  
Farzad Rahmani ◽  
Abolfazl Nosrati-Tirkani ◽  
Shima Mehrabadi ◽  
Hamid Fiuji ◽  
...  

Abstract Background : The Wnt/beta-catenin pathway is dysregulated in pancreatic cancer and is reported to be associated with poor prognosis, indicating the need for identification of novel agents to improve the efficacy of current therapy or have better activity. Therefore in the present study we explored the anticancer activity of PNU-74654 alone or in combination with gemcitabine in 2 and 3 dimensional cell culture model of pancreatic cancer. Methods: The MTT assay was applied to determine the viability of PC cancerous cells (PCC), while the cytotoxicity of this agent was evaluated in 3D cell culture model (spheroid). The effects of PNU-74654 was investigated in established cell migration/invasion assays. Result: The expression of candidate genes affecting the cell cycle, migration, and Wnt/b-catenin pathway was evaluated at mRNA and/or proteins by RT-PCR or Western blot. PNU-74654 inhibited the cell growth at IC50 of 122±0.4 umol/L, and had a synergistic effect on the antiproliferative properties of gemcitabine by modulating the Wnt pathway. The PNU-74654/gemcitabine combination reduced the migratory and invasiveness of PC cells, compared to control cells through perturbation of E-cadherin. Conclusion: In aggregate our findings demonstrated the profound antitumor properties of PNU-74654 in pancreatic cancer, supporting further studies to evaluate the therapeutic impact of this novel therapy to target Wnt pathway in the treatment of pancreatic cancer.


2004 ◽  
Vol 171 (4S) ◽  
pp. 295-295
Author(s):  
Fernando C. Delvecchio ◽  
Ricardo M. Brizuela ◽  
Karen J. Byer ◽  
W. Patrick Springhart ◽  
Saeed R. Khan ◽  
...  

Pathogens ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 9
Author(s):  
Donghoon Kang ◽  
Natalia V. Kirienko

Pseudomonas aeruginosa is a multidrug-resistant, opportunistic pathogen that utilizes a wide-range of virulence factors to cause acute, life-threatening infections in immunocompromised patients, especially those in intensive care units. It also causes debilitating chronic infections that shorten lives and worsen the quality of life for cystic fibrosis patients. One of the key virulence factors in P. aeruginosa is the siderophore pyoverdine, which provides the pathogen with iron during infection, regulates the production of secreted toxins, and disrupts host iron and mitochondrial homeostasis. These roles have been characterized in model organisms such as Caenorhabditis elegans and mice. However, an intermediary system, using cell culture to investigate the activity of this siderophore has been absent. In this report, we describe such a system, using murine macrophages treated with pyoverdine. We demonstrate that pyoverdine-rich filtrates from P. aeruginosa exhibit substantial cytotoxicity, and that the inhibition of pyoverdine production (genetic or chemical) is sufficient to mitigate virulence. Furthermore, consistent with previous observations made in C. elegans, pyoverdine translocates into cells and disrupts host mitochondrial homeostasis. Most importantly, we observe a strong correlation between pyoverdine production and virulence in P. aeruginosa clinical isolates, confirming pyoverdine’s value as a promising target for therapeutic intervention. This in vitro cell culture model will allow rapid validation of pyoverdine antivirulents in a simple but physiologically relevant manner.


2013 ◽  
Vol 45 (4) ◽  
pp. 325 ◽  
Author(s):  
Anurupa Maitra ◽  
Shahnaz Patel ◽  
VijayR Bhate ◽  
VilliS Toddywalla ◽  
MaithiliA Athavale

PLoS ONE ◽  
2012 ◽  
Vol 7 (4) ◽  
pp. e35008 ◽  
Author(s):  
Elhaseen Elamin ◽  
Daisy Jonkers ◽  
Kati Juuti-Uusitalo ◽  
Sven van IJzendoorn ◽  
Freddy Troost ◽  
...  

2019 ◽  
Vol 64 (2) ◽  
pp. 112-123 ◽  
Author(s):  
Teruo Miyazaki ◽  
Akira Honda ◽  
Tadashi Ikegami ◽  
Takashi Iida ◽  
Yasushi Matsuzaki

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