Pancreatic Cell News Volume 8.15 | Apr 18 2017

TOP STORY

What Makes Pancreatic Cancer So Aggressive?

Pancreatic cancer is one of the most aggressive tumor types because it starts forming metastases early. The cancer itself, however, is usually only discovered late. This leads to a high patient mortality rate. Researchers have discovered why pancreatic cancer and other malignant types of tumors can disseminate so rapidly. [Press release from the Friedrich-Alexander-Universität discussing online prepublication in Nature Cell Biology] Press Release | Abstract

(Ranked by impact factor of the journal)

DIABETES & PANCREATITIS

β Cell Aging Markers Have Heterogeneous Distribution and Are Induced by Insulin Resistance

Scientists hypothesized that the heterogeneity of pancreatic β cells is due to subpopulations of β cells at different stages of their life cycle with different functional capacities and that further changes occur with metabolic stress and aging. They identified new markers of aging in β cells, including IGF1R. In β cells IGF1R expression correlated with age, dysfunction, and expression of known age markers p16^ink4a, p53BP1, and senescence-associated β-galactosidase. [Cell Metab] Abstract | Press Release | Graphical Abstract

An Activating STAT3 Mutation Causes Neonatal Diabetes through Premature Induction of Pancreatic Differentiation

The authors investigated the effect of an activating mutation, STAT3^K392R, on pancreatic development using induced pluripotent stem cells derived from a patient with neonatal diabetes and pancreatic hypoplasia. Early pancreatic endoderm differentiated similarly from STAT3^K392R and healthy-control cells, but in later stages, NEUROG3 expression was upregulated prematurely in STAT3^K392R cells together with insulin and glucagon. [Cell Rep] Full Article | Graphical Abstract

Advances in Pancreatic Islet Monolayer Culture on Glass Surfaces Enable Super-Resolution Microscopy and Insights into Beta Cell Ciliogenesis and Proliferation

Guided by an observation that dispersed islet cells spread and adhere well on glass surfaces in neuronal co-culture and form a monolayer of connected cells, investigators demonstrated that in the absence of neurons, well-defined surface coatings combined with components of neuronal culture media collectively support robust attachment and growth of primary human or rat islet cells as monolayers on glass surfaces. [Sci Rep] Full Article

Novel ATP-Synthase Independent Mechanism Coupling Mitochondrial Activation to Exocytosis in Insulin-Secreting Cells

To elucidate how mitochondrial activation in beta-cells contributes to insulin secretion, scientists compared the effects of glucose and the mitochondrial substrate methylsuccinate in INS-1E insulin secreting cells, at the respective concentrations they maximally activate mitochondrial respiration. Both substrates induced insulin secretion with distinct respiratory profiles, mitochondrial hyperpolarization, NADH production and ATP/ADP ratios. [J Cell Sci] Abstract | Full Article

Laser Capture Microdissection of Pancreatic Acinar Cells to Identify Proteomic Alterations in a Murine Model of Caerulein-Induced Pancreatitis

Investigators hypothesized that pancreatic acinar regions contain proteomic signatures relevant to disease processes, including secreted proteins that could be detected in biofluids. Consistent with pathogenesis, they observed increases in proteins related to fibrosis, several proteases, and altered expression of proteins associated with diminished pancreas function. [Clin Transl Gastroenterol] Full Article

PANCREATIC CANCER

Tumor-Penetrating Peptide Enhances Transcytosis of Silicasome-Based Chemotherapy for Pancreatic Cancer

In a KRAS-induced orthotopic pancreatic ductal adenocarcinoma model, coadministration of iRGD enhanced the uptake of an irinotecan-loaded silicasome carrier that comprises lipid bilayer–coated mesoporous silica nanoparticles; this uptake resulted in enhanced survival and markedly reduced metastasis. [J Clin Invest] Full Article | Press Release

Therapeutic Effects of Argyrin F in Pancreatic Adenocarcinoma

Investigators hypothesized that Argyrin F (AF) may prevent pancreatic ductal adenocarcinoma (PDAC) progression. They used PDAC cells and engineered mice to assess AF anticancer activity. AF inhibited cell proliferation, migration, invasion and colony formation in vitro. [Cancer Lett] Abstract

Asporin Promotes Pancreatic Cancer Cell Invasion and Migration by Regulating the Epithelial-to-Mesenchymal Transition (EMT) through Both Autocrine and Paracrine Mechanisms

Asporin expression in pancreatic stellate cells (PSCs) and its roles in PSC-pancreatic cancer cell (PCC) interaction remain unclear. The authors showed that Asporin is highly expressed in activated PSCs and is involved in PSC-mediated invasion and migration of PCCs. [Cancer Lett] Abstract

Inhibition of DNA2 Nuclease as a Therapeutic Strategy Targeting Replication Stress in Cancer Cells

Researchers demonstrated that DNA2 is overexpressed in pancreatic cancers, one of the deadliest and more aggressive forms of human cancers, where mutations in the KRAS are present in 90–95% of cases. Depletion of DNA2 significantly reduced pancreatic cancer cell survival and xenograft tumor growth. [Oncogenesis] Full Article

Comprehensive Dissection of Transcriptome Data and Regulatory Factors in Pancreatic Cancer Cells

Scientists performed a comprehensive analysis using 282 pancreatic tumor and normal samples from seven independent expression data sets to provide a better view on the interactions between different transcription factors and the most affected biological pathways in pancreatic cancer. They highlighted common differentially expressed genes and common affected processes within pancreatic cancer samples. [J Cell Biochem] Abstract

The Islet Endothelial Cell: A Novel Contributor to Beta Cell Secretory Dysfunction in Diabetes

The authors examine potential candidate molecules that may mediate the positive effects of islet endothelial cells on beta cell survival and function under normal conditions. [Diabetologia] Abstract

Oncolytic Viral Therapy for Pancreatic Cancer

Oncolytic viruses represent an emerging class of immunotherapeutic agents that have undergone extensive preclinical investigation and warrant further investigation in well-designed clinical trials. [J Surg Oncol] Abstract

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

OncoMed’s Phase II Demcizumab Pancreatic Cancer Trial Misses Primary Endpoint

OncoMed Pharmaceuticals, Inc. reported top-line results from the company’s Phase II YOSEMITE clinical trial of demcizumab in combination with Abraxane^® plus gemcitabine in previously untreated patients with metastatic pancreatic cancer. The trial did not meet the primary endpoint of progression-free survival. [OncoMed Pharmaceuticals, Inc.] Press Release

Granite Donates $5 Million More to Defeat Cancer

Granite Telecommunications, LLC announced that it has given $5 million to the Dana-Farber Cancer Institute. [Granite Telecommunications, LLC] Press Release

Republican Scientists Negotiate the Trump Era

Conservative academics face a growing tension between their politics and the liberal atmosphere on many US campuses. [Nature News] Editorial

French-Election Fears Unite Scientists in Defense of Liberal Democracy

For scientists in France, the presidential contest is often a chance to debate research and science-related issues. When Nicolas Sarkozy was elected a decade ago, for example, university reforms and environmental policy featured prominently in the campaigns. But this time, science has barely been mentioned — elbowed out by political scandals and the rise of Marine Le Pen’s far-right Front National party. [Nature News] Editorial

With This New System, Scientists Never Have to Write a Grant Application Again

Almost every scientist agrees: Applying for research funding is a drag. Writing a good proposal can take months, and the chances of getting funded are often slim. Funding agencies, meanwhile, spend more and more time and money reviewing growing stacks of applications. That’s why two researchers are proposing a radically different system that would do away with applications and reviews; instead scientists would just give each other money. [ScienceInsider] Editorial

NEW Protein Aggregation in Health and Disease
June 11-16, 2017
Steamboat Springs, United States

NEW Rapid Signaling and Genomic Steroid Hormone Actions in Health and Disease
June 11-16, 2017
Snowmass Village, United States

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NEW Postdoctoral Fellow – Diabetes (University of Toronto)

NEW Postdoctoral Associate – Pancreatic Beta Cells (Johns Hopkins School of Medicine)

NEW Faculty Member – Endocrinology, Diabetes and Metabolism (Johns Hopkins University)

NEW Professorship – Molecular Endocrinology (Ludwig-Maximilians-Universität München)

Senior Scientist – Pancreatic Cell Research (STEMCELL Technologies Inc.)

Cell Biology Scientist – Autoimmune Disease (Immunocore)

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

Postdoctoral Fellow – Diabetes Research (Child Health Institute of New Jersey)

Principle Investigator – Human Physiology and Experimental Medicine (University of Cambridge)

Postdoctoral Fellow – Prostate/Pancreatic Cancer (Medical College of Wisconsin)

Postdoctoral Positions – Life Sciences (Helmholtz Zentrum München)

Associate Program Officer – Type 1 Diabetes (Helmsley Charitable Trust)

Postdoctoral Fellows – Diabetes Research (Icahn School of Medicine at Mount Sinai)

Postdoctoral Fellow – Beta Cell Biology (CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences)

Principle Scientist – Translational Development (Celgene Corporation)

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