Volume 5.43 | Nov 18

Pancreatic Cell News 5.43 November 18, 2014
Pancreatic Cell News
     In this issue: Publications | Reviews | Industry News | Policy News | Events | Jobs
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TOP STORY
Long-Term Persistence and Development of Induced Pancreatic Beta Cells Generated by Lineage Conversion of Acinar Cells
Using an improved method for in vivo conversion of adult mouse pancreatic acinar cells toward beta cells, scientists show that induced beta cells persist for up to 13 months (the length of the experiment), form pancreatic islet-like structures and support normoglycemia in diabetic mice. [Nature Biotech]
Abstract | Press Release
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PUBLICATIONS (Ranked by impact factor of the journal)
DIABETES & PANCREATITIS

Diabetes Enhances the Proliferation of Adult Pancreatic Multipotent Progenitor Cells and Biases Their Differentiation to More β-Cell Production
Researchers show that β-cell metabolic stress and hyperglycemia enhance the proliferation capacities of adult pancreatic multipotent progenitors cells and bias their production of progeny towards β-cells in mouse and human. [Diabetes] Abstract

CTGF Modulates Adult β-Cell Maturity and Proliferation to Promote β-Cell Regeneration in Mice
Investigators discovered that in embryos, connective tissue growth factor (CTGF) is necessary for β-cell proliferation, and increased CTGF in β-cells promotes proliferation of immature insulin+ cells. CTGF over-expression, under non-stimulatory conditions, does not increase adult β-cell proliferation. [Diabetes] Abstract

Retinoic Acid Receptor Signaling Is Required to Maintain Glucose-Stimulated Insulin Secretion and β-Cell Mass
Retinoic acid signaling is required for maintaining a range of cellular processes, including cell differentiation, proliferation, and apoptosis. The authors investigated the actions of all-trans-retinoic acid signaling in pancreatic β-cells of adult mice. [FASEB J] Abstract

MiR-200 Is Induced by Thioredoxin-Interacting Protein and Regulates ZEB1 Signaling and Beta Cell Apoptosis
Using INS-1 beta cells as well as primary islets, scientists discovered that expression of miR-200 was induced by thioredoxin-interacting protein and by diabetes. They found that miR-200 targeted and decreased zinc finger E-box binding homeobox 1 (Zeb1) and promoted beta cell apoptosis as measured by cleaved caspase-3 levels, Bax/Bcl2 ratio, and TUNEL. [J Biol Chem] Abstract | Full Article | Press Release

Deletion of Apoptosis Signal-Regulating Kinase 1 (ASK1) Protects Pancreatic Beta-Cells from Stress-Induced Death but Not from Glucose Homeostasis Alterations under Pro-Inflammatory Conditions
Researchers tested whether ASK1 deficiency protects beta-cells from glucolipotoxic conditions and cytokines treatment or from glucose homeostasis alteration induced by endotoxemia. [PLoS One] Full Article

Oxygen Supply by Photosynthesis to an Implantable Islet Cell Device
Recently, scientists developed an immunoisolated chamber system for transplantation of human islets without immunosuppression. This system depended on daily oxygen supply. To provide independence from this external source, they incorporated a novel approach based on photosynthetically-generated oxygen.
[Horm Metab Res]
Abstract

PANCREATIC CANCER

LASP1 Is a HIF-1α Target Gene Critical for Metastasis of Pancreatic Cancer
Investigators report that LASP1 is overexpressed in pancreatic ductal adenocarcinoma (PDAC) where it promotes invasion and metastasis. They found that LASP1 overexpression in PDAC cells was mediated by HIF-1α through direct binding to a hypoxia response element in the LASP1 promoter. [Cancer Res] Abstract

Curaxin CBL0137 Eradicates Drug Resistant Cancer Stem Cells and Potentiates Efficacy of Gemcitabine in Preclinical Models of Pancreatic Cancer
The efficacy of CBL0137 alone or in combination with current standard of care, gemcitabine, was tested against different models of pancreatic ductal adenocarcinoma in vitro and in mouse models. It was found that CBL0137 alone is a potent inducer of apoptosis in pancreatic cancer cell lines and is toxic not only for proliferating bulk tumor cells, but also for pancreatic cancer stem cells [Oncotarget] Full Article

Pharmacological Inhibition and Genetic Knockdown of EPAC1 Reduce Pancreatic Cancer Metastasis In Vivo
Scientists investigated the role of EPAC1 in invasion and metastasis of pancreatic ductal adenocarcinoma in vivo, and evaluated the therapeutic potential of EPAC inhibitors as anti-metastasis agents for this neoplasm. [Mol Pharmacol] Abstract | Full Article

Effects of Insulin on Human Pancreatic Cancer Progression Modeled In Vitro
Researchers examined the effects of a range of insulin doses on signaling, proliferation and survival in three human cell models meant to represent three stages in pancreatic cancer progression: primary pancreatic duct cells, the HPDE immortalized pancreatic ductal cell line, and the PANC1 metastatic pancreatic cancer cell line. [BMC Cancer] Full Article

Downregulation of CPE Regulates Cell Proliferation and Chemosensitivity in Pancreatic Cancer
The expressions of carboxypeptidase E (CPE) in pancreatic cancer (PC) cell lines and cancer patients were investigated by Western blot and qRT-PCR. In PC cell line BX-pc-3, CPE was downregulated and its effect on cancer cell proliferation, migration, cisplatin chemosensitivity, and in vivo tumor growth was analyzed by Western blot, proliferation assay, invasion assay, and in vivo transplantation, respectively. [Tumor Biol] Abstract

Free Cell Stem Cell Poster: Directed Differentiation of ESCs/iPSCs
 
REVIEWS
Recent Advances in Cell Replacement Therapies for the Treatment of Type 1 Diabetes
Isolated islet (or whole pancreas) transplantation, xenotransplantation, and the transplant of human pluripotent stem cell-derived β-cells provide the potential to restore endogenous insulin production and re-establish normoglycemia. The authors discuss the latest advances in these fields, including the use of encapsulation technology, as well as some of the hurdles that still need to be overcome for these alternative therapies to become mainstream and/or progress to clinical development. [Endocrinology] Abstract | Full Article

MicroRNA Function in Pancreatic β Cells
The author focuses on microRNAs (miRNAs) with important roles in regulation of insulin production, insulin secretion, and β-cell development, and will discuss only miRNAs with established roles in β-cell function.
[Mol Endocrinol]
Abstract | Full Article

Visit our reviews page to see a complete list of reviews in the pancreatic cell research field.
 
INDUSTRY NEWS
FDA Grants Orphan Drug Designation to Merrimack Pharmaceuticals’ MM-141 for the Treatment of Pancreatic Cancer
Merrimack Pharmaceuticals, Inc. announced that the U.S. Food and Drug Administration (FDA) has granted orphan drug designation to their investigational drug candidate MM-141 for the treatment of pancreatic cancer. MM-141 is a tetravalent bispecific antibody designed to block tumor survival signals by targeting receptor complexes containing IGF-1R and ErbB3. [Merrimack Pharmaceuticals, Inc.] Press Release

PCRF Funds New Research Worth £1.2 Million
The Pancreatic Cancer Research Fund (PCRF) has invested £1.2 million into seven ambitious new projects to tackle the UK’s deadliest cancer. This is the second year that PCRF has invested over £1 million in a single funding round, enabling innovative research that could lead to new treatments for this highly aggressive and complex cancer. [Pancreatic Cancer Research Fund] Press Release

ViaCyte Receives U.S. Patent Claiming Alternative Methods to Manufacture Pancreatic Progenitor Cells In Vitro
ViaCyte, Inc. announced it has been granted U.S. patent 8,859,286, which describes methods for manufacture of human pancreatic progenitor cells from definitive endoderm cells. [ViaCyte, Inc.] Press Release

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POLICY NEWS
National Institutes of Health (United States)

Food and Drug Administration (United States)

Center for Biologics Evaluation and Research (United States)

European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

Therapeutic Goods Administration (Australia)
 
EVENTS
NEW Advances in Cancer Immunotherapy 2014
December 5, 2014
Tampa, United States

Visit our events page to see a complete list of events in the pancreatic cell community.
 
JOB OPPORTUNITIES
NEW Postdoctoral Researcher – Chromatin and Epigenetic Regulation (Van Andel Research Institute)

NEW Head of Cellular and Molecular Therapies Laboratory (NHS Blood & Transplant)

Postdoctoral Position – Cancer Drug Delivery (University of Tartu)

PhD Studentship – Driving Cells Towards a Pancreatic Fate (University of Edinburgh)

Postdoctoral Position – Endothelial Dysfunction and Diabetes (Weill Cornell Medical College in Qatar)

Associate or Full Professor – Pediatric Diabetes and Metabolic Disease (University of California San Diego)

Postdoctoral Fellowship Position – Obesity and Diabetes Pathogenesis (NIDDK / NIH)

Research Assistant – Diabetes/Metabolic Health (The Nestlé Institute of Health Sciences)

Full or Associate Professor – Endocrinology, Diabetes and Metabolism (University of Pennsylvania)

Scientist – Pluripotent Stem Cell Biology Endoderm Lineages (STEMCELL Technologies Inc.)

Scientist – Pluripotent Stem Cell Media Development, High Throughput Screening (STEMCELL Technologies Inc.)

Scientist – Cell Culture Support Products (STEMCELL Technologies Inc.)

Scientist – Immunology/Cell Separation (STEMCELL Technologies Inc.)

Research Associate – Cell Separation (STEMCELL Technologies Inc.)


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