Zucara Therapeutics Doses First Subject in Phase I Trial of ZT-01

Zucara Therapeutics, Inc., a diabetes life sciences company developing the first once-daily therapeutic to prevent insulin-induced hypoglycemia, announced that it has dosed the first subject in its Phase I trial of ZT-01.
[Zucara Therapeutics, Inc.]
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Cdc6 Disruption Leads to Centrosome Abnormalities and Chromosome Instability in Pancreatic Cancer Cells

Cell division cycle 6 (Cdc6)-depleted pancreatic cancer cells significantly inhibited cell proliferation and colony formation, delayed G2/M cell cycle progression, and increased expression of p-histone H3 and cyclin A2 levels.
[Scientific Reports]
Youn, Y., Lee, J., Kim, J., Kim, J. H., & Hwang, J.-H. (2020). Cdc6 disruption leads to centrosome abnormalities and chromosome instability in pancreatic cancer cells. Scientific Reports, 10(1), 16518. https://doi.org/10.1038/s41598-020-73474-6 Cite
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Single-Cell Transcriptome Analysis of Tumor and Stromal Compartments of Pancreatic Ductal Adenocarcinoma Primary Tumors and Metastatic Lesions

Investigators employed a single-cell RNA sequencing technology to profile the transcriptomes of individual cells from dissociated primary tumors or metastatic biopsies obtained from patients with pancreatic ductal adenocarcinoma.
[Genome Medicine]
Lin, W., Noel, P., Borazanci, E. H., Lee, J., Amini, A., Han, I. W., Heo, J. S., Jameson, G. S., Fraser, C., Steinbach, M., Woo, Y., Fong, Y., Cridebring, D., Von Hoff, D. D., Park, J. O., & Han, H. (2020). Single-cell transcriptome analysis of tumor and stromal compartments of pancreatic ductal adenocarcinoma primary tumors and metastatic lesions. Genome Medicine, 12(1), 80. https://doi.org/10.1186/s13073-020-00776-9 Cite
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Pancreatic Cancer Cells Require the Transcription Factor MYRF to Maintain ER Homeostasis

Investigators found that pancreatic ductal adenocarcinomas overexpressed the myelin regulatory factor, an ER membrane-associated transcription factor released by self-cleavage.
[Developmental Cell]
Milan, M., Balestrieri, C., Alfarano, G., Polletti, S., Prosperini, E., Nicoli, P., Spaggiari, P., Zerbi, A., Cirulli, V., Diaferia, G. R., & Natoli, G. (2020). Pancreatic Cancer Cells Require the Transcription Factor MYRF to Maintain ER Homeostasis. Developmental Cell, 0(0). https://doi.org/10.1016/j.devcel.2020.09.011 Cite
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Topologically Selective Islet Vulnerability and Self-Sustained Downregulation of Markers for β-Cell Maturity in Streptozotocin-Induced Diabetes

Scientists showed that hyperglycemic Streptozotocin-treated mice still harbor a large pool of remaining β-cells but displayed pancreas-wide downregulation of glucose transporter type 2. Islet gene expression studies confirmed this downregulation and revealed impaired β-cell maturity.
[Communications Biology]
Hahn, M., van Krieken, P. P., Nord, C., Alanentalo, T., Morini, F., Xiong, Y., Eriksson, M., Mayer, J., Kostromina, E., Ruas, J. L., Sharpe, J., Pereira, T., Berggren, P.-O., Ilegems, E., & Ahlgren, U. (2020). Topologically selective islet vulnerability and self-sustained downregulation of markers for β-cell maturity in streptozotocin-induced diabetes. Communications Biology, 3(1), 1–14. https://doi.org/10.1038/s42003-020-01243-2 Cite
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Genetic Variant Effects on Gene Expression in Human Pancreatic Islets and Their Implications for T2D

The authors explored the relationship between genetic variants influencing predisposition to type 2 diabetes and related glycemic traits, and human pancreatic islet transcription using data from 420 donors.
[Nature Communications]
Viñuela, A., Varshney, A., van de Bunt, M., Prasad, R. B., Asplund, O., Bennett, A., Boehnke, M., Brown, A. A., Erdos, M. R., Fadista, J., Hansson, O., Hatem, G., Howald, C., Iyengar, A. K., Johnson, P., Krus, U., MacDonald, P. E., Mahajan, A., Manning Fox, J. E., … McCarthy, M. I. (2020). Genetic variant effects on gene expression in human pancreatic islets and their implications for T2D. Nature Communications, 11(1), 4912. https://doi.org/10.1038/s41467-020-18581-8 Cite
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Tumor-Associated Macrophages Derived from Cancer Stem Cells

This study displayed histological and immunohistochemical analyses of a malignant tumor model developed from cancer stem cells converted from human iPSCs in a cancer microenvironment prepared from the conditioned medium of a pancreatic cancer cell line.
[Acta Histochemica]
Osman, A., Oze, M., Afify, S. M., Hassan, G., EL-Ghlban, S., Nawara, H. M., Fu, X., Zahra, M. H., Seno, A., Winer, I., Salomon, D. S., & Seno, M. (2020). Tumor-associated macrophages derived from cancer stem cells. Acta Histochemica, 122(8), 151628. https://doi.org/10.1016/j.acthis.2020.151628 Cite
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Human Pancreatic Cancer Cells under Nutrient Deprivation Are Vulnerable to Redox System Inhibition

Researchers determined that some small molecular compounds, such as penicillic acid, papyracillic acid, and auranofin, exhibited preferential cytotoxicity to human pancreatic cancer cells under nutrient-deprived compared with nutrient-sufficient conditions.
[Journal of Biological Chemistry]
Onodera, T., Momose, I., Adachi, H., Yamazaki, Y., Sawa, R., Ohba, S., & Kawada, M. (2020). Human pancreatic cancer cells under nutrient deprivation are vulnerable to redox system inhibition. Journal of Biological Chemistry, jbc.RA120.013893. https://doi.org/10.1074/jbc.RA120.013893 Cite
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AXIM® Biotechnologies Receives Notice of US Patent Allowance for Proprietary Compounds and Methods Targeting Tumor Metastasis Through QSOX1

AXIM® Biotechnologies, Inc. announced that the United States Patent and Trademark Office has issued the company a new Notice of Allowance for a patent on anti-neoplastic compounds and methods targeting Quiescin Sulfhydryl Oxidase 1, an enzyme important for tumor cell growth, invasion and metastasis.
[ AXIM Biotechnologies, Inc.]
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Genomic and Epigenomic Landscaping Defines New Therapeutic Targets for Adenosquamous Carcinoma of the Pancreas

Scientists interrogated purified sorted tumor fractions from a series of 15 tumor samples with whole-genome copy-number variant, whole-exome sequencing, and assay for transposase-accessible chromatin using sequencing analyses.
[Cancer Research]
Lenkiewicz, E., Malasi, S., Hogenson, T. L., Flores, L. F., Barham, W., Phillips, W. J., Roesler, A. S., Chambers, K. R., Rajbhandari, N., Hayashi, A., Antal, C. E., Downes, M., Grandgenett, P. M., Hollingsworth, M. A., Cridebring, D., Xiong, Y., Lee, J.-H., Ye, Z., Yan, H., … Barrett, M. T. (2020). Genomic and Epigenomic Landscaping Defines New Therapeutic Targets for Adenosquamous Carcinoma of the Pancreas. Cancer Research. https://doi.org/10.1158/0008-5472.CAN-20-0078 Cite
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Modulation of Rab7a-Mediated Growth Factor Receptor Trafficking Inhibits Islet Beta Cell Apoptosis and Autophagy Under Conditions of Metabolic Stress

Investigators explored the novel hypothesis that regulation of growth factor receptor trafficking can be used to promote islet beta cell survival. Growth factor signaling was dependent on the presence of cell surface receptors.
[Scientific Reports]
Hewawasam, N. V., Lhaf, F., Taylor, H. A., Viloria, K., Austin, A., King, A., Jones, P., Jones, L., Turner, M. D., & Hill, N. J. (2020). Modulation of Rab7a-mediated growth factor receptor trafficking inhibits islet beta cell apoptosis and autophagy under conditions of metabolic stress. Scientific Reports, 10(1), 15741. https://doi.org/10.1038/s41598-020-72939-y Cite
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