miR-124 or EZH2 was overexpressed in AsPC-1 and PANC1 cells. Then, the effects on cell viability, apoptosis, invasion, migration and epithelial mesenchymal transition were evaluated. The roles of miR-124 on the expression and function of EZH2 in pancreatic tumors were determined by dual luciferase reporter assay. Subsequently, miR-124 was transfected to bone marrow mesenchymal stromal cells (BM-MSCs), and the BM-MSCs derived exosomes were isolated and co-cultured with AsPC-1 and PANC1 cells, or injected into pancreatic cancer tumor-bearing mice.
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Apexigen, Inc. announced that the US FDA has granted orphan drug designation status to APX005M for the treatment of esophageal and gastroesophageal junction cancer and for the treatment of pancreatic cancer.
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Scientists found a consistent, abnormal methylation pattern in insulinomas. They found that abnormal insulin (INS) promoter methylation and altered transcription factor expression created alternative drivers of INS expression, replacing canonical PDX1-driven beta cell specification with a pathological, looping, distal enhancer-based form of transcriptional regulation.
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Karakose, E., Wang, H., Inabnet, W., Thakker, R. V., Libutti, S., Fernandez-Ranvier, G., Suh, H., Stevenson, M., Kinoshita, Y., Donovan, M., Antipin, Y., Li, Y., Liu, X., Jin, F., Wang, P., Uzilov, A., Argmann, C., Schadt, E. E., Stewart, A. F., … Lambertini, L. (2020). Aberrant methylation underlies insulin gene expression in human insulinoma. Nature Communications, 11(1), 5210. https://doi.org/10.1038/s41467-020-18839-1 Cite
The authors focus on three types of well-established ncRNAs — microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) — and discuss their potential as diagnostic, prognostic and predictive biomarkers in pancreatic ductal adenocarcinoma.
[Seminars in Cancer Biology]
Researchers demonstrated that somatostatin and glucagon secretion were linked in a reciprocal feedback cycle with somatostatin inhibiting glucagon secretion at low and high glucose levels, and glucagon stimulating somatostatin secretion via the glucagon and GLP-1 receptors.
Plasma glucagon responses during hyperinsulinemic-hypoglycemic clamps (40 mg/dL) were assessed in dogs with spontaneous diabetes (n=13) and healthy non-diabetic dogs (n=6). Plasma C-peptide responses to intravenous glucagon were measured to assess endogenous insulin secretion. Plasma pancreatic polypeptide, epinephrine and norepinephrine were measured as indices of parasympathetic and sympathoadrenal autonomic responses to insulin-induced hypoglycemia.
[American Journal of Physiology-Endocrinology and Metabolism]
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Co-impairment of autonomic and glucagon responses to insulin-induced hypoglycemia in dogs with naturally-occurring insulin-dependent diabetes mellitus | American Journal of Physiology-Endocrinology and Metabolism. (n.d.). Retrieved October 13, 2020, from https://journals.physiology.org/doi/abs/10.1152/ajpendo.00379.2020 Cite
Scientists report that leptin augments NMDA subtype of glutamate receptors function via Src kinase-mediated phosphorylation of the GluN2A subunit.
[Journal of Biological Chemistry]
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Cochrane, V. A., Wu, Y., Yang, Z., ElSheikh, A., Dunford, J., Kievit, P., Fortin, D. A., & Shyng, S.-L. (2020). Leptin modulates pancreatic β-cell membrane potential through Src kinase-mediated phosphorylation of NMDA receptors. Journal of Biological Chemistry, jbc.RA120.015489. https://doi.org/10.1074/jbc.RA120.015489 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
Nanobiotix announced that the first patient has been injected in its phase I study evaluating NBTXR3 activated by radiation therapy for patients with pancreatic cancer.
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Investigators used sublines to screen molecular targets for the treatment of pancreatic cancer. Among the genes with increased expression levels in the sublines, they focused on those encoding cell surface receptors that may be involved in the interactions between cancer cells and the tumor microenvironment.
The authors analyze the role of cancer associated fibroblasts (CAFs) in therapeutic resistance of pancreatic cancer and discuss potential CAFs-targeting strategies basing on the diverse biological functions of CAFs, thus to improve the outcome of pancreatic cancer treatment.
[Biochimica et Biophysica Acta-Reviews On Cancer]
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Han, X., Zhang, W.-H., Wang, W.-Q., Yu, X.-J., & Liu, L. (2020). Cancer-associated fibroblasts in therapeutic resistance of pancreatic cancer: Present situation, predicaments, and perspectives. Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, 1874(2), 188444. https://doi.org/10.1016/j.bbcan.2020.188444 Cite