Pancreatic Cell News Volume 8.23 | Jun 13 2017

TOP STORY

Innovative Therapy Strategy for Pancreatic Cancer Uses Engineered Exosomes Targeting Mutated KRAS Gene

Genetic manipulation of exosomes, virus-sized particles released by all cells, may offer a new therapeutic approach to treating pancreatic cancer, according to researchers. Earlier investigations demonstrated exosomes as a factor in detecting pancreatic cancer, but these latest findings reveal genetically altered exosomes as a potentially novel approach for direct and specific targeting of mutated KRAS, the cancer gene commonly linked to pancreatic cancer. [Press release from MD Anderson Cancer Center discussing online prepublication in Nature] Press Release | Abstract

(Ranked by impact factor of the journal)

DIABETES & PANCREATITIS

N-Acyl Taurines and Acylcarnitines Cause an Imbalance in Insulin Synthesis and Secretion Provoking β Cell Dysfunction in Type 2 Diabetes

Investigators examined the pathophysiology of β cells under type 2 diabetes progression directly in pancreatic tissues. They used MALDI imaging of Langerhans islets within mouse tissues or from human tissues to generate in situ-omics data, which they supported with in vitro experiments. [Cell Metab] Abstract | Press Release | Graphical Abstract

Amino Acid Transporter Slc38a5 Controls Glucagon Receptor Inhibition-Induced Pancreatic α Cell Hyperplasia in Mice

Researchers demonstrated that glucagon pathway blockade selectively increases expression of the sodium-coupled neutral amino acid transporter Slc38a5 in a subset of highly proliferative α cells and that Slc38a5 controls the pancreatic response to glucagon pathway blockade; most notably, mice deficient in Slc38a5 exhibit markedly decreased α cell hyperplasia to glucagon pathway blockade-induced hyperaminoacidemia. [Cell Metab] Abstract | Graphical Abstract

Sox5 Regulates Beta-Cell Phenotype and Is Reduced in Type 2 Diabetes

The authors showed that a set of co-expressed genes, which is enriched for genes with islet-selective open chromatin, is associated with type 2 diabetes (T2D). These genes are perturbed in T2D and have a similar expression pattern to that of dedifferentiated islets. [Nat Commun] Full Article | Press Release

Raptor Regulates Functional Maturation of Murine Beta Cells

Scientists showed that deletion of Raptor, which is an essential component of mTORC1, in insulin-expressing cells promotes hypoinsulinemia and glucose intolerance. Raptor-deficient beta cells displayed reduced glucose responsiveness and exhibited a glucose metabolic profile resembling fetal beta cells. [Nat Commun] Full Article

Long-Term Culture of Self-Renewing Pancreatic Progenitors Derived from Human Pluripotent Stem Cells

Investigators developed culture conditions that support long-term self-renewal of human multipotent pancreatic progenitors, which are developmentally more proximal to the specialized cells of the adult pancreas. These cultured pancreatic progenitor cells expressed key pancreatic transcription factors, including PDX1 and SOX9, and exhibited transcriptomes closely related to their in vivo counterparts [Stem Cell Reports] Full Article

NAD⁺ Augmentation Ameliorates Acute Pancreatitis through Regulation of Inflammasome Signaling

The authors investigated the effect of increased cellular nicotinamide adenine dinucleotide (NAD)⁺ levels on cerulein-induced acute pancreatitis (AP). They demonstrated for the first time that the activities and expression of SIRT1 were suppressed by reduction of intracellular NAD⁺ levels and the p53-microRNA-34a pathway in cerulein-induced AP. [Sci Rep] Full Article

PANCREATIC CANCER

BRM/SMARCA2 Promotes the Proliferation and Chemoresistance of Pancreatic Cancer Cells by Targeting JAK2/STAT3 Signaling

BRM shRNA reduced the proliferation and increased the sensitivity of pancreatic cancer cells to gemcitabine in vivo and in vitro, and these effects are associated with the inhibition of STAT3 phosphorylation and reduced transcription of STAT3 target genes. [Cancer Lett] Abstract

KIF15 Promotes Pancreatic Cancer Proliferation via the MEK–ERK Signaling Pathway

KIF15 was upregulated in human pancreatic cancer tissues, and higher KIF15 expression levels correlated with shorter patient survival times. Upregulation KIF15 promoted pancreatic cancer growth. KIF15 upregulated cyclin D1, CDK2, and phospho-RB and also promoted G1/S transition in pancreatic cancer cells. [Br J Cancer] Abstract

The G2 Checkpoint Inhibitor CBP-93872 Increases the Sensitivity of Colorectal and Pancreatic Cancer Cells to Chemotherapy

To examine the potential use of CBP-93872 for clinical applications, scientists analyzed the synergistic effects of platinum-containing drugs, oxaliplatin and cisplatin, pyrimidine antimetabolites, gemcitabine and 5-fluorouracil, in combination with CBP-93872, on cell lethality in colorectal and pancreatic cancer cell lines. [PLoS One] Full Article

Pancreatic Stellate Cells: What’s New?

Pancreatic stellate cells (PSCs) play an integral role in the pathogenesis of pancreatitis and pancreatic cancer. With the developing knowledge of this important cell type, researchers are at the cusp of developing effective therapies for the above diseases based upon targeting the PSC and modulating its function. [Curr Opin Gastroenterol] Abstract

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

Lilly Announces Strategic Collaboration with KeyBioscience AG

Eli Lilly and Company and KeyBioscience AG have agreed to a new collaboration focused on the development of dual amylin calcitonin receptor agonists, a potential new class of treatments for metabolic disorders such as type 2 diabetes, the companies announced. [Eli Lilly and Company] Press Release

NantKwest Expands NANT Cancer Vaccine Program with Additional Clinical Trials Announced Addressing Multiple Cancer Types across All Stages of Disease

NantKwest and Nantworks announced the expansion of the company’s existing NANT Cancer Vaccine program in pancreatic cancer to target a number of additional tumor types. [NantKwest] Press Release

Can Fake Names Tease Out NIH Reviewer Bias?

When the label “white male” is attached to a research grant application, do peer reviewers give it a better score? That’s the question psychologist Patricia Devine of the University of Wisconsin in Madison has spent the past four years, and more than $1 million from the National Institutes of Health (NIH) in Bethesda, Maryland, trying to answer with an unusual experiment. [ScienceInsider] Editorial

Curiosity and Irritation Meet Macron’s Effort to Lure Foreign Scientists to France

The French government unveiled a website aimed at attracting foreign scientists with four-year grants worth up to €1.5 million each. [ScienceInsider] Editorial

Trump Names Sharpless to Lead U.S. Cancer Institute

President Donald Trump announced his intention to appoint Norman “Ned” Sharpless to be the next director of the National Cancer Institute in Bethesda, Maryland. Sharpless, who is 50 years old, is a physician and currently director of the Lineberger Comprehensive Cancer Center at the University of North Carolina in Chapel Hill. He also holds an academic appointment at the university’s school of medicine. [ScienceInsider] Editorial

NEW ASCO/AACR Methods in Clinical Cancer Research Workshop
July 29-August 4, 2017
Vail, Colorado, United States

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

NEW Postdoctoral Scholarship – Diabetes Research (Lund University)

NEW Postdoctoral Position – Pancreatic Cell Research (Inserm)

Postdoctoral Research Fellow – Pancreatic Cancer (Fred Hutchinson Cancer Research Center)

PhD Position – Insulin Storage (Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences)

PhD Position – Health/Biomedical Sciences (University of Auckland)

Postdoctoral Position – Metabolic Regulation of Embryonic and Stem Cells (Joslin Diabetes Center)

Postdoctoral Fellowship – Diabetes UK (Diabetes UK)

PhD Studentship – Diabetes UK (Diabetes UK)

Assistant/ Associate Professor – Type 1 Diabetes Clinical and Basic Science (University of Colorado Anschutz Medical Campus)

Postdoc Position – Cellular Modeling of Diabetes Risk Variants Using Pluripotent Stem Cells (University of California, San Diego)

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