Pancreatic Cell News Volume 9.23 | Jun 12 2018

TOP STORY

Cigarette Smoke Induces Stem Cell Features of Pancreatic Cancer Cells via PAF1

Chronic exposure of HPNE and Capan1 cells to cigarette smoke extract caused them to increase markers of stem cells, including autofluorescence and sphere formation, compared to control cells. Exposure of cells to nicotine and nicotine-derived carcinogens led to increased expression of cholinergic receptor nicotinic alpha 7 subunit, FOS like 1, AP-1 transcription factor subunit, and polymerase II-associated factor (PAF1) along with stem cell features. [Gastroenterology] Abstract

(Ranked by impact factor of the journal)

DIABETES & PANCREATITIS

A Novel Inhibitor of iNOS Dimerization Protects against Cytokine-Induced Rat β-Cell Dysfunction

Scientists reported that a novel small molecule, ATV399, was identified from a high content image-based screen for compounds that inhibit cleaved caspase-9 activation and subsequent β-cell apoptosis induced by a combination of IL-1β, IFN-γ and high glucose, which together mimicked the pathogenic diabetic milieu. [Br J Pharmacol] Abstract

Metabolic Activation-Driven Mitochondrial Hyperpolarization Predicts Insulin Secretion in Human Pancreatic Beta-Cells

The author showed that glucose-induced mitochondrial membrane potential (MMP) hyperpolarization is necessary for, and predicts, the rate of insulin secretion in primary cultured human beta-cells. When glucose concentration was elevated, increased metabolism resulted in a substantial MMP hyperpolarization, as well as in increased rates of ATP synthesis and turnover marked by faster cell respiration. [Biochim Biophys Acta] Abstract

Critical Role for the Tsc1-mTORC1 Pathway in β-Cell Mass in Pdx1 Deficient Mice

Scientists knocked down pancreatic duodenal homeobox (Pdx1) gene expression in mouse MIN6 insulinoma cells. Pdx1 suppression not only increased apoptotic cell death but also decreased cell proliferation, which was associated with a decrease in activity of mechanistic target of rapamycin complex 1 (mTORC1). [J Endocrinol] Abstract

The P2X7 Receptor and Pannexin-1 Are Involved in Glucose-Induced Autocrine Regulation in β-Cells

Researchers showed that glucose induced rapid release of ATP and a significant fraction of that release involved the P2X7 receptor and pannexin-1, both expressed in INS-1E cells, rat and mouse β-cells. They also provide pharmacological evidence that extracellular ATP, via P2X7 receptor, stimulated Ca²⁺ transients and cell proliferation in INS-1E cells and insulin secretion in INS-1E cells and rat islets. [Sci Rep] Full Article

Chemokine CXCL16 Mediates Acinar Cell Necrosis in Cerulein Induced Acute Pancreatitis in Mice

Investigators revealed lower expression of Ccl9, a neutrophil chemoattractant, in the pancreatic acini of Cxcl16^−/− mice than wild type mice. Ccl9 mRNA expression was induced by stimulation with Cxcl16 protein in pancreatic acinar cells in vitro, suggesting a Cxcl16/Ccl9 cascade. [Sci Rep] Full Article

PANCREATIC CANCER

Hypoxic Tumor-Derived Exosomal miR-301a Mediates M2 Macrophage Polarization via PTEN/PI3Kγ to Promote Pancreatic Cancer Metastasis

Investigators found that hypoxic exosomes derived from pancreatic cancer (PC) cells activated macrophages to the M2 phenotype in a HIF-1a or HIF-2a-dependent manner, which then facilitated the migration, invasion, and EMT of PC cells. They discovered that miR-301a-3p was highly expressed in hypoxic PC cells and enriched in hypoxic PC cells-derived exosomes. [Cancer Res] Abstract | Full Article

A CRISPR-Cas13a System for Efficient and Specific Therapeutic Targeting of Mutant KRAS for Pancreatic Cancer Treatment

The authors showed that the bacterial Cas13a protein and crRNA significantly knocked down mutant KRAS mRNA expression, identifying a CRISPR-Cas13a system that can induce up to a 94% knockdown efficiency. CRISPR-Cas13a-mediated KRAS-G12D mRNA knockdown potently induced apoptosis in vitro and elicited marked tumor shrinkage in mice. [Cancer Lett] Abstract

The Development of [18F]AlF-NOTA-NT as PET Agents of Neurotensin Receptor-1 Positive Pancreatic Cancer

Scientists reported the simple preparation of Aluminum-18F-NOTA-neurotensin (NT) starting from aqueous 18F. Cell binding test demonstrated that [19F]AlF-NOTA-NT maintained high receptor-binding affinity to NT receptor 1. [Mol Pharm] Abstract

TRAIL/NF-κB/CX3CL1 Mediated Onco-Immuno Crosstalk Leading to TRAIL Resistance of Pancreatic Cancer Cell Lines

The chemokine CX3CL1 was established as a central NF-κB target gene mediating therapy resistance. While no direct impact of CX3CL1 expression on cancer cell apoptosis was identified in co-culture assays it became apparent that CX3CL1 was acting in a paracrine fashion, leading to an increased recruitment of inflammatory cells. These inflammatory cells in turn mediated apoptosis resistance of pancreatic ductal adenocarcinoma cells. [Int J Mol Sci] Full Article

Signal-Targeted Therapies and Resistance Mechanisms in Pancreatic Cancer: Future Developments Reside in Proteomics

The authors discuss the current state of clinical trials for targeted therapies against pancreatic cancer, highlight the most recent proteomic data for pancreatic tumors and their metastasis, which could help to identify major oncogenic signaling dependencies, as well as provide future leads to explain why pancreatic tumors are intrinsically resistant to signal-targeted therapies. [Cancers] Full Article

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

New Late-Breaking Data on the Use of Type 2 Diabetes Treatment Invokana^® (Canagliflozin) in the Real World Will Be Presented

The Janssen Pharmaceutical Companies of Johnson & Johnson announced that a new late-breaking analysis examining how INVOKANA^® and other type 2 diabetes therapies are being used by U.S. patients is among the 15 company abstracts accepted for oral and poster presentations. [Press release from Janssen Global Services, LLC discussing research to be presented at the American Diabetes Association’s (ADA) 78^th Annual Scientific Sessions, Orlando] Press Release

New Center for Advanced Regenerative Engineering Launches

Northwestern’s newest center has officially launched with a bold mission and interdisciplinary mindset. The Center for Advanced Regenerative Engineering aims to create an ecosystem that enables researchers and clinicians to regenerate tissues and organs for adult and pediatric patients. [McCormick School of Engineering, Northwestern University] Press Release

National Cancer Institute Selects ASU to Lead Revolutionary Research in Cancer

Arizona State University (ASU) has been awarded more than $8.5 million over five years from the National Cancer Institute to establish the Arizona Cancer and Evolution Center. The grant will establish ASU as the hub of an international network of research scientists who are dedicated to understanding cancer in an entirely new way. [Arizona State University] Press Release

Targovax Tumbles after Chemotherapy Cocktail Data Dent Pancreatic Cancer Plans

Targovax has hit pause on its neoantigen vaccine R&D strategy after seeing independent data that will redefine the standard of care in resected pancreatic cancer. The leap forward in the treatment of the disease forced Targovax to rethink its strategy and pull out of a planned Phase II trial. [Targovax (FierceBiotech)] Press Release

Sexual Harassment Is Rife in the Sciences, Finds Landmark US Study

The analysis concludes that policies to fight the problem are ineffective because they are set up to protect institutions, not victims — and that universities, funding agencies, scientific societies and other organizations must take stronger action. [Nature News] Editorial

North American Universities Increasingly Cancel Publisher Packages

Florida State University will head into negotiations with the publisher Elsevier to see how it can resolve a pricing issue. The university’s move represents the latest example of academic libraries walking away from these comprehensive and expensive subscriptions, which include all or most of a publisher’s catalog, and instead signing up for a la carte titles. [The Scientist] Editorial

Leading Salk Scientist Resigns after Allegations of Harassment

The prominent cancer biologist Inder Verma unconditionally resigned from the Salk Institute for Biological Studies in San Diego, California, June 6, and the research institute’s board of trustees voted unanimously to accept his resignation. [ScienceInsider] Editorial

China Introduces Sweeping Reforms to Crack Down on Academic Misconduct

China is getting tough on scientific misconduct. The country’s most powerful bodies, the Chinese Communist Party and the State Council, introduced a raft of reforms on 30 May aimed at improving integrity across the research spectrum, from funding and job applications to peer-review and publications. [Nature News] Editorial

More Restrictive U.S. Policy on Chinese Graduate Student Visas Raises Alarm

Reversing yet another policy of the previous administration, the U.S. Department of State began applying tougher restrictions on some Chinese graduate students. The new policy shortens from five years to one year the duration of visas for those planning to study aviation, robotics, and advanced manufacturing. [ScienceInsider] Editorial

NEW The American Society for Cell Biology (ASCB) Annual Meeting 2018
December 8-12, 2018
San Diego, California, United States

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

NEW Assistant or Associate Professor (Tenure Track) – Immunopathology of Metabolic Diseases (University of British Columbia)

NEW Postdoctoral Research Scientist – Metabolic Homeostasis Research (London Institute of Medical Sciences)

Postdoctoral Position – Human Pluripotent Stem Cell-Based Cell Therapy in Type 1 Diabetes (University of Copenhagen)

Postdoctoral Fellowship – Pancreatic Cancer (European Molecular Biology Laboratory)

Postdoctoral Researcher – Pancreatic Islets & Beta Cell Transplantation (Karolinska Institutet)

Postdoctoral Positions – Translational Diabetes Research (Partner of German Center for Diabetes Research)

Postdoctoral Fellow – Microfluidic Modeling of Type 2 Diabetes (Karolinska Institutet)

Postdoctoral Scholars – Structural Biology (The University of Chicago)

EBPOD Fellowship – Pancreatic Cancer Analysis (European Molecular Biology Laboratory)

Postdoctoral Positions – Immunology of Diabetes (Cochin Institute)

Postdoctoral Position – Functional Genomics of Insulin Resistance (Stanford University)

Postdoctoral Fellows – Diabetes Complications & Epigenetics (St. Michael’s Hospital)

Doctoral Thesis Positions – Diabetes Research (International Helmholtz Research School for Diabetes)

Doctoral Thesis Position – Genomics of Pancreatic Cancer and Pancreatic Development (Universitatsklinikum Ulm)

Associate Professor or Professor – Biomedical Metabolics (The Ohio State University Wexner Medical Center)

Postdoctoral Scholar – Glucose Homeostasis, Obesity & Type 2 Diabetes (University of California – San Francisco)

Postdoctoral Fellow – Molecular Medicine (City of Hope)

Doctoral Thesis Position – Endocrine Cell Research (Helmholtz Zentrum Munchen)

Doctoral Thesis Position – Diabetes Research (Universite Libre de Bruxelles)

Pioneer Award Postdoctoral Fellowships – Pancreatic Cancer (University of Miami Miller School of Medicine)

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

Postdoctoral Fellow – Epigenetic Regulation of Pancreatic Beta-Cell Mass (City of Hope)

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.