Cultured primary PDA cells expressed Rgs16::GFP in response to cytotoxic drugs. A histone deacetylase inhibitor, TSA, stimulated Rgs16::GFP expression in PDA primary cells, potentiated gemcitabine and JQ1 cytotoxicity in cell culture, and Gem + TSA + JQ1 inhibited tumor initiation and progression in vivo.
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Layeghi-Ghalehsoukhteh, S., Pal Choudhuri, S., Ocal, O., Zolghadri, Y., Pashkov, V., Niederstrasser, H., Posner, B. A., Kantheti, H. S., Azevedo-Pouly, A. C., Huang, H., Girard, L., MacDonald, R. J., Brekken, R. A., & Wilkie, T. M. (2020). Concerted cell and in vivo screen for pancreatic ductal adenocarcinoma (PDA) chemotherapeutics. Scientific Reports, 10(1), 20662. https://doi.org/10.1038/s41598-020-77373-8 Cite
Researchers showed that the miRNA cargo of extracellular vesicles (EVs) from pancreatic ductal adenocarcinoma organoids largely differs among patients. However, they detected a common set of EV miRNAs that were present in matched organoids and blood plasma samples of individual patients.
[Cellular and Molecular Life Sciences]
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Zeöld, A., Sándor, G. O., Kiss, A., Soós, A. Á., Tölgyes, T., Bursics, A., Szűcs, Á., Harsányi, L., Kittel, Á., Gézsi, A., Buzás, E. I., & Wiener, Z. (2020). Shared extracellular vesicle miRNA profiles of matched ductal pancreatic adenocarcinoma organoids and blood plasma samples show the power of organoid technology. Cellular and Molecular Life Sciences. https://doi.org/10.1007/s00018-020-03703-8 Cite
Potential regulatory proteins in pancreatitis were identified by proteomic screen using pancreatic tissues of PRSS1Tg AP mice. Adenoviral shRNA-mediated knockdown of identified proteins, followed by functional assays was performed to validate their roles.
[Cell Death & Disease]
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Tan, J., Cao, R., Zhou, L., Zhou, Z., Chen, H., Xu, J., Chen, X., Jin, Y., Lin, J., Qi, Z., Zeng, J., Li, S., Luo, M., Hu, G., Jin, J., & Zhang, G. (2020). EMC6 regulates acinar apoptosis via APAF1 in acute and chronic pancreatitis. Cell Death & Disease, 11(11), 1–13. https://doi.org/10.1038/s41419-020-03177-3 Cite
Mechanistically, Hic-5 knock down significantly inhibited the TGF-β/Smad2 signaling pathway, resulting in reduced collagen production and α-smooth muscle actin expression in the activated pancreatic stellate cells.
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Gao, L., Lei, X.-F., Miyauchi, A., Noguchi, M., Omoto, T., Haraguchi, S., Miyazaki, T., Miyazaki, A., & Kim-Kaneyama, J. (2020). Hic-5 is required for activation of pancreatic stellate cells and development of pancreatic fibrosis in chronic pancreatitis. Scientific Reports, 10(1), 19105. https://doi.org/10.1038/s41598-020-76095-1 Cite
Investigators generated a mouse model with pancreas-specific deletion of PKD3, the predominant PKD isoform in mouse pancreatic acinar cells, by crossing Pkd3flox/flox mice with Pdx1-Cre transgenic mice which express Cre recombinase under the control of the mouse Pdx1 promoter.
[Biochimica Et Biophysica Acta-Molecular Basis of Disease]
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Yuan, J., Chheda, C., Piplani, H., Geng, M., Tan, G., Thakur, R., & Pandol, S. J. (2020). Pancreas-specific deletion of protein kinase D attenuates inflammation, necrosis, and severity of acute pancreatitis. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 165987. https://doi.org/10.1016/j.bbadis.2020.165987 Cite
The authors discuss the use of dipeptidyl peptidase 4 inhibitors (DPP4i) in the treatment of type 2 diabetes mellitus, highlighting their benefits and risks. They focus primarily on the five DPP4i with the widest geographical distribution.
[Nature Reviews Endocrinology]
Compromised gustatory sensing, achieved by Gnat3 ablation, enhanced the CXCL1/2 – CXCR2 axis to alter the myeloid-derived suppressor cell population and promoted the progression of metastatic pancreatic ductal adenocarcinoma.
[Cellular and Molecular Gastroenterology and Hepatology]
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Hoffman, M. T., Kemp, S. B., Salas-Escabillas, D. J., Zhang, Y., Steele, N. G., The, S., Long, D., Benitz, S., Yan, W., Margolskee, R. F., Bednar, F., Pasca di Magliano, M., Wen, H.-J., & Crawford, H. C. (2020). The Gustatory Sensory G-Protein GNAT3 Suppresses Pancreatic Cancer Progression in Mice. Cellular and Molecular Gastroenterology and Hepatology. https://doi.org/10.1016/j.jcmgh.2020.08.011 Cite
Scientists studied the role of extracellular cold-inducible RNA-binding protein, a novel damage-associated-molecular-pattern molecule, in severe acute pancreatitis.
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Linders, J., Madhi, R., Rahman, M., Mörgelin, M., Regner, S., Brenner, M., Wang, P., & Thorlacius, H. (2020). Extracellular cold-inducible RNA-binding protein regulates neutrophil extracellular trap formation and tissue damage in acute pancreatitis. Laboratory Investigation, 1–13. https://doi.org/10.1038/s41374-020-0469-5 Cite
Scientists showed that low expression of κB-Ras GTPases was frequently detected in pancreatic ductal adenocarcinoma and correlated with higher histologic grade.
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The authors’ microarray analysis of pancreatic tissues from mild and severe acute pancreatitis mice models identified angiopoietin‐like 4 (ANGPTL 4) as one of the most significantly upregulated genes.
[EMBO Molecular Medicine]
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The expression of IL-5R and the effects of IL-5 were analyzed in human and murine tumor cells.
[Cell Communication and Signaling]
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