Concerted Cell and In Vivo Screen for Pancreatic Ductal Adenocarcinoma (PDA) Chemotherapeutics

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.
[Scientific Reports]
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
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Shared Extracellular Vesicle miRNA Profiles of Matched Ductal Pancreatic Adenocarcinoma Organoids and Blood Plasma Samples Show the Power of Organoid Technology

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]
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
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EMC6 Regulates Acinar Apoptosis via APAF1 in Acute and Chronic Pancreatitis

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]
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
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Hic-5 Is Required for Activation of Pancreatic Stellate Cells and Development of Pancreatic Fibrosis in Chronic Pancreatitis

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.
[Scientific Reports]
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
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Pancreas-Specific Deletion of Protein Kinase D Attenuates Inflammation, Necrosis, and Severity of Acute Pancreatitis

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]
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
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Dipeptidyl Peptidase 4 Inhibitors in the Treatment of Type 2 Diabetes Mellitus

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]
Deacon, C. F. (2020). Dipeptidyl peptidase 4 inhibitors in the treatment of type 2 diabetes mellitus. Nature Reviews Endocrinology, 1–12. https://doi.org/10.1038/s41574-020-0399-8 Cite
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The Gustatory Sensory G-Protein GNAT3 Suppresses Pancreatic Cancer Progression in Mice

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]
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
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Extracellular Cold-Inducible RNA-Binding Protein Regulates Neutrophil Extracellular Trap Formation and Tissue Damage in Acute Pancreatitis

Scientists studied the role of extracellular cold-inducible RNA-binding protein, a novel damage-associated-molecular-pattern molecule, in severe acute pancreatitis.
[Laboratory Investigation]
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
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κB-Ras and Ral GTPases Regulate Acinar to Ductal Metaplasia during Pancreatic Adenocarcinoma Development and Pancreatitis

Scientists showed that low expression of κB-Ras GTPases was frequently detected in pancreatic ductal adenocarcinoma and correlated with higher histologic grade.
[Nature Communications]
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ANGPTL 4 Exacerbates Pancreatitis by Augmenting Acinar Cell Injury through Upregulation of C5a

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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Identification of a Novel IL-5 Signaling Pathway in Chronic Pancreatitis and Crosstalk with Pancreatic Tumor Cells

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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