Pancreatic Cell News Volume 9.38 | Sep 25 2018

TOP STORY

Discovering Human Diabetes-Risk Gene Function with Genetics and Physiological Assays

Loss of BCL11A, a transcriptional regulator, in primary human islet cells led to enhanced insulin secretion. Gene expression profiling revealed BCL11A-dependent regulation of multiple genes involved in insulin exocytosis. [Nat Commun] Full Article

(Ranked by impact factor of the journal)

DIABETES & PANCREATITIS

Lineage Dynamics of Murine Pancreatic Development at Single-Cell Resolution

The authors found a previously undescribed endocrine progenitor population, as well as an analogous population in both human fetal tissue and human embryonic stem cells differentiating toward a pancreatic beta cell fate. They identified candidate transcriptional regulators along the differentiation trajectory of this population toward the alpha or beta cell lineages. [Nat Commun] Full Article

Pancreatic β-Cell tRNA Hypomethylation and Fragmentation Link TRMT10A Deficiency with Diabetes

Researchers confirmed the role of TRMT10A as a guanosine 9 transfer RNA (tRNA) methyltransferase, and identified tRNA^Gln and tRNA^iMeth as two of its targets. [Nucleic Acids Res] Full Article

RB1CC1-Enhanced Autophagy Facilitates PSCs Activation and Pancreatic Fibrogenesis in Chronic Pancreatitis

Retinoblastoma coiled coil protein 1 (RB1CC1) was positively correlated with pancreatic fibrogenesis in tissues and plasma of chronic pancreatitis patients. Knockdown of RB1CC1 restrained alpha smooth muscle actin and collagen expressions, and autophagy in activated pancreatic stellate cells (PSCs) in vitro. [Cell Death Dis] Full Article

Long-Term Culture and In Vitro Maturation of Macroencapsulated Adult and Neonatal Porcine Islets

Pig islets survived longer and secreted more insulin when cultured on acellular porcine dermis compared to human fascia. Islets from neonatal pigs could survive up to 33 weeks in vitro, and their insulin secretion increased during the first five weeks of culture in a beta-cell maturation medium. [Xenotransplantation] Abstract

PANCREATIC CANCER

Tobacco Carcinogen-Induced Production of GM-CSF Activates CREB to Promote Pancreatic Cancer

Smokers had significantly higher levels of activated cAMP response element-binding protein (CREB) when compared to non-smokers. Cell lines derived from normal pancreas and pancreatic intraepithelial neoplasm exhibited low baseline pCREB levels compared to pancreatic cancer cell lines. [Cancer Res] Abstract | Full Article

Inhibition of 15-PGDH Causes Kras-Driven Tumor Expansion through Prostaglandin E2-ALDH1 Signaling in the Pancreas

Scientists demonstrated that pharmacological inhibition of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) enhanced CYP26A1 expression, leading to depletion of all-trans retinoic acid and expansion of the ALDH1-positive subset in both human PDAC cells and tumor cells of Kras^LSL-G12D/+; Ptf1a^Cre/+ mice. [Oncogene] Abstract

Melittin-Induced Long Non-Coding RNA NONHSAT105177 Inhibits Proliferation and Migration of Pancreatic Ductal Adenocarcinoma

Investigators found that melittin treatment increased NONHSAT105177 expression in pancreatic ductal adenocarcinoma (PDAC) cell lines but not in normal pancreatic ductal epithelial cell line. Overexpression of NONHSAT105177 inhibited PDAC cell proliferation, migration, and the epithelial-mesenchymal transition, both in vitro and in vivo. [Cell Death Dis] Full Article

Effects of Repurposed Drug Candidates Nitroxoline and Nelfinavir as Single Agents or in Combination with Erlotinib in Pancreatic Cancer Cells

When used as single agents, nelfinavir and nitroxoline decreased viability, affected cell cycle and reduced the expression of relevant cell cycle proteins. The effects on apoptosis were variable among pancreatic cancer (PC) cell lines. These agents drastically impaired clonogenic activity of the three PC cell lines. [J Exp Clin Cancer Res] Abstract

Visualizing the Dynamics of Live Pancreatic Microtumors Self-Organized through Cell-in-Cell Invasion

When pancreatic ductal adenocarcinoma cells were cultured on a micro/nanoplate overnight, the cells self-organized into non-spheroidal microtumors that were anchored to the micro/nanoplate through cell-in-cell invasion. This self-organization was only efficiently induced in small-diameter rough microislands. [Sci Rep] Full Article | Press Release

Subscribe to one of our other 19 science newsletters such as Hepatic Cell News & Intestinal Cell News.

Does Axl Have Potential as a Therapeutic Target in Pancreatic Cancer?

Investigators provide an overview of Axl and its function in normal conditions, summarize the regulation and function of Axl in cancer, and highlight the contribution of Axl to pancreatic cancer as well as its potential as a therapeutic target. [Expert Opin Ther Targets] Abstract

Targeting Protein Misfolding to Protect Pancreatic Beta-Cells in Type 2 Diabetes

The author reviews mechanisms known to contribute to protein misfolding and formation of toxic oligomers, and the deleterious consequences of these oligomers on beta-cell function and survival. [Curr Opin Pharmacol] Abstract

Visit our reviews page to see a complete list of reviews in the pancreatic cell research field.

BioXcel Therapeutics Expands Immuno-Oncology Partnership with Nektar into Clinical Development in Pancreatic Cancer

The collaboration will clinically evaluate the novel combination of BTI’s BXCL701, a small molecule immune-modulator, DPP 8/9 and FAP inhibitor; Nektar’s NKTR-214, a CD122-biased agonist; and a checkpoint inhibitor as a potential therapy for pancreatic cancer. [BioXcel Therapeutics Inc.] Press Release

ERYTECH Announces Enrollment of First Patients in Phase III Clinical Trial Evaluating Eryaspase for the Treatment of Second Line Pancreatic Cancer

ERYTECH Pharma announced that the first three patients have been enrolled in its pivotal Phase III clinical trial, named ‘TRYbeCA1’, evaluating its lead product candidate eryaspase for the treatment of second line metastatic pancreatic cancer. [Erytech Pharma] Press Release

Farxiga Achieved a Positive Result in the Phase III DECLARE-TIMI 58 Trial, a Large Cardiovascular Outcomes Trial in 17,000 Patients with Type-2 Diabetes

AstraZeneca announced positive results from the Phase III DECLARE-TIMI 58 cardiovascular outcomes trial (CVOT) for Farxiga, the broadest SGLT2 inhibitor CVOT conducted to date. [AstraZeneca] Press Release

Lustgarten Foundation Advances Pancreatic Cancer Research through Partnerships with the Opening of Two New Laboratories

The Lustgarten Foundation announced two new pancreatic cancer research laboratories through respective partnerships with Dana-Farber Cancer Institute and Massachusetts Institute of Technology. The opening of these Lustgarten Foundation Pancreatic Cancer Research Laboratories will usher in a new era of research progress and represents an initial $10 million investment. [The Lustgarten Foundation] Press Release

Trump Administration Launches Review of Scientific Research Involving Fetal Tissue

The Trump administration has launched a comprehensive review of all research that involves fetal tissue, reopening an issue that has galvanized anti-abortion activists but worried scientists who fear their work could be under threat. [STAT News] Editorial

More and More Scientists Are Preregistering Their Studies. Should You?

Preregistration, in its simplest form, is a one-page document answering basic questions such as: What question will be studied? What is the hypothesis? What data will be collected, and how will they be analyzed? In its most rigorous form, a “registered report,” researchers write an entire paper, minus the results and discussion, and submit it for peer review at a journal, which decides whether to accept it in principle. [ScienceInsider] Editorial

NEW 17^th World Congress of the International Pancreas & Islet Transplant Association (IPITA 2019)
July 2-5, 2019
Lyon, France

Visit our events page to see a complete list of events in the community.

NEW Postdoctoral Researcher – Identifying Cell Surface Receptor (Ionis Pharmaceuticals, Inc.)

Research Technologist – Pancreatic (STEMCELL Technologies Inc.)

Postdoctoral Position – Metabolic Inflammation in Diabetes (Inserm)

Assistant Professor – Biomedical Sciences (New York Institute of Technology)

Scientists – Diabetes Research (Qatar Biomedical Research Institute)

Postdoctoral Position – Human Microphysiology Systems of Pancreatic Islets (University of Pittsburgh Drug Discovery Institute)

Caspar Wistar Fellows – Cancer Biology (The Wistar Institute)

Postdoctoral Researcher – Diabetes Research (UC San Diego School of Medicine)

Postdoctoral Associate – Protein-Protein Interactions in Islets (Stanford Burmham Prebys Medical Discovery Institute)

Postdoctoral Associate – Biology of the Pancreas and Diabetes (University of Minnesota)

Assistant/Associate/Full Professor – Diabetes & Neuroscience (Indiana University School of Medicine)

Postdoctoral Positions – Immunology of Diabetes (Cochin Institute)

Postdoctoral Position – Inflammation and Metabolism (Sanford Burnham Prebys Medical Discovery Institute)

Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.

Have we missed an important article or publication in Pancreatic Cell News? Click here to submit!

Comments or suggestions? Submit your feedback here.