Investigators cover the accumulating data about the roles of the bromodomain and extraterminal domain (BET) family in innate immunity, and discuss the attractive prospect of manipulating the BET family as a new treatment for disease.
[Signal Transduction and Targeted Therapy]
The authors highlight research that has led to a new understanding of retinal pathophysiology during diabetes mellitus and that has uncovered potential new therapeutic avenues to treat this debilitating disease.
[Nature Reviews Endocrinology]
Scientists evaluated improvements to therapeutic efficacy through combination therapy incorporating NanoKnife and M1 virus. They showed that irreversible electroporation triggered reactive oxygen species-dependent apoptosis in pancreatic cancer cells mediated by phosphatidylinositol-3-kinase/protein kinase B pathway suppression.
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Sun, S., Liu, Y., He, C., Hu, W., Liu, W., Huang, X., Wu, J., Xie, F., Chen, C., Wang, J., Lin, Y., Zhu, W., Yan, G., Cai, J., & Li, S. (2021). Combining NanoKnife with M1 oncolytic virus enhances anticancer activity in pancreatic cancer. Cancer Letters, 502, 9–24. https://doi.org/10.1016/j.canlet.2020.12.018 Cite
Scientists evaluated the efficacy of TR1801-ADC, a newly developed ADC composed of a MET antibody conjugated to the highly potent pyrrolobenzodiazepine toxin-linker Tesirine. They first evaluated MET expression and subcellular localization in pancreatic cancer cell lines, human tumors and patient derived xenografts.
[Clinical Cancer Research]
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Cazes, A., Betancourt, O., Esparza, E., Mose, E. S., Jaquish, D., Wong, E., Wascher, A. A., Tiriac, H., Gymnopoulos, M., & Lowy, A. M. (2021). A MET Targeting Antibody-Drug Conjugate Overcomes Gemcitabine Resistance in Pancreatic Cancer. Clinical Cancer Research. https://doi.org/10.1158/1078-0432.CCR-20-3210 Cite
A descriptive analysis of parietal epithelial cells was undertaken in diabetic db/db mice and in diabetic patients.
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Kawaguchi, T., Hasegawa, K., Yasuda, I., Muraoka, H., Umino, H., Tokuyama, H., Hashiguchi, A., Wakino, S., & Itoh, H. (2021). Diabetic condition induces hypertrophy and vacuolization in glomerular parietal epithelial cells. Scientific Reports, 11(1), 1515. https://doi.org/10.1038/s41598-021-81027-8 Cite
Dermal fibroblasts (DF) are critical for effective wound healing, so the authors sought to establish whether there were any differences in DF cultured from Type 2 diabetes mellitus donors or those without diabetes.
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Al-Rikabi, A. H. A., Tobin, D. J., Riches-Suman, K., & Thornton, M. J. (2021). Dermal fibroblasts cultured from donors with type 2 diabetes mellitus retain an epigenetic memory associated with poor wound healing responses. Scientific Reports, 11(1), 1474. https://doi.org/10.1038/s41598-020-80072-z Cite
Scientists generated human cancer cell lines of pancreatic and lung origin carrying an inducible shRNA against NRF2 and PERK. They report that PERK-related phosphorylation of NRF2 was only critical in Keap1 wildtype cells to escape its degradation, but showed no direct effect on nuclear import or transcriptional activity of NRF2.
[Cell Death & Disease]
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Küper, A., Baumann, J., Göpelt, K., Baumann, M., Sänger, C., Metzen, E., Kranz, P., & Brockmeier, U. (2021). Overcoming hypoxia-induced resistance of pancreatic and lung tumor cells by disrupting the PERK-NRF2-HIF-axis. Cell Death & Disease, 12(1), 1–11. https://doi.org/10.1038/s41419-020-03319-7 Cite
NantKwest, Inc. and ImmunityBio, Inc. announced early interim results of its PD-L1 t-haNK protocols showing median survival rates more than doubled that of the historic rate in patients with advanced metastatic pancreatic cancer for which no other FDA-approved treatment exists.
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The authors focus on TGFB1/INHBA homodimer/Nodal-SMAD2/3 signaling network in pancreatic cancer as a pivotal central node which regulates multiple key mechanisms involved in the development of chemoresistance, including enhancement of the stem cell-like properties and tumorigenicity of pancreatic cancer cells, mediating cooperative interactions between pancreatic cancer cells and the surrounding stroma as well as regulating the deposition of ECM proteins within the tumor microenvironment.
Adocia announced it has developed a hydrogel scaffold that hosts and protects pancreatic β cells for replacement of the missing cells of people with type 1 diabetes.
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Scientists developed a stable β-cell line that retains the characteristics of mature β-cells.
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Establishment of a long-term stable β-cell line and its application to analyze the effect of Gcg expression on insulin secretion | Scientific Reports. (n.d.). Retrieved January 12, 2021, from https://www.nature.com/articles/s41598-020-79992-7 Cite