Pancreatic Cell News Volume 5.39 | Oct 14 2014

α1-Antitrypsin Modifies General NK Cell Interactions with Dendritic Cells and Specific Interactions with Islet β-Cells in Favor of Protection from Autoimmune Diabetes
Scientists demonstrate that α1-antitrypsin (AAT) significantly reduces NK cell degranulation against β-cells, albeit in the whole animal and not in isolated NK cell cultures. AAT-treated mice, and not isolated cultured β-cells, exhibited a marked reduction in NKp46 ligand levels on β-cells. [Immunology] Abstract

Cytoskeletal Dependence of Insulin Granule Movement Dynamics in INS-1 Beta-Cells in Response to Glucose
For pancreatic β-cells to secrete insulin in response to elevated blood glucose, insulin granules retained within the subplasmalemmal space must be transported to sites of secretion on the plasma membrane. Using a combination of super-resolution STORM imaging and live cell TIRF microscopy scientists investigated how the organization and dynamics of the actin and microtubule cytoskeletons in INS-1 β-cells contribute to this process. [PLoS One] Full Article

Conditionally Immortalized Human Pancreatic Stellate Cell Lines Demonstrate Enhanced Proliferation and Migration in Response to IGF-I
Researchers generated conditionally immortalized human non-tumor and tumor-derived pancreatic stellate cells via transformation with the temperature-sensitive SV40 large T antigen and human telomerase. [Exp Cell Res] Full Article

Myocardin and Pdx-1 Synergistically Induce hMSCs to Differentiate into Insulin Secreting Cells
Scientists report a new method to induce the differentiation of human mesenchymal stem cells (hMSCs) into insulin secretion cells. The method is cotransduction of myocardin and pdx-1 for seven days. [Biochem Biophys Res Commun] Abstract

PANCREATIC CANCER

c-Rel Is a Critical Mediator of NF-κB-Dependent TRAIL Resistance of Pancreatic Cancer Cells
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-resistant cells exhibited a strong TRAIL-inducible NF-κB activity, whereas TRAIL-sensitive cells displayed only a small increase in NF-κB-binding activity. Transfection with siRNA against c-Rel sensitized the TRAIL-resistant cells in a manner comparable to siRNA targeting the p65/RelA subunit. [Cell Death Dis] Full Article

Mutated K-ras Activates CDK8 to Stimulate the Epithelial-to-Mesenchymal Transition in Pancreatic Cancer in Part via the Wnt/β-Catenin Signaling Pathway
Researchers demonstrate that mutated K-ras stimulates cyclin-dependent kinase 8 (CDK8) expression, possibly by regulating HIF-1α, and both CDK8 and mutated K-ras were confirmed to promote cell proliferation and prevent apoptosis in vitro. Additionally, they found that both CDK8 and mutated K-ras promote the invasion and migration of pancreatic cancer cells via the positive regulation of the Wnt/β-catenin signaling pathway [Cancer Lett] Abstract

Inhibition of Protein Phosphatase 2A Sensitizes Pancreatic Cancer to Chemotherapy by Increasing Drug Perfusion via HIF-1α-VEGF Mediated Angiogenesis
Researchers used a small molecular compound LB-100 to assess the effect of pharmacological inhibition of protein phosphatase 2A in combination with doxorubicin on the proliferation of pancreatic cancer in cell lines and a xenograft model. [Cancer Lett] Abstract

A New Goniothalamin N-Acylated Aza-Derivative Strongly Downregulates Mediators of Signaling Transduction Associated with Pancreatic Cancer Aggressiveness
Despite the fact that goniothalamin and its derivative caused pancreatic cancer cell cycle arrest and cell death, only the derivative was able to downregulate pro-survival and proliferation pathways mediated by mitogen activated protein kinase ERK1/2. [Eur J Med Chem] Abstract

Growth Hormone Receptor Inhibition Decreases the Growth and Metastasis of Pancreatic Ductal Adenocarcinoma
Scientists used an RNA interference approach targeted to growth hormone receptor (GHR) to determine whether targeting GHR is an effective method for controlling pancreatic cancer growth and metastasis. For this, they used an in vitro model system consisting of HPAC and PANC-1 pancreatic cancer cells lines. [Exp Mol Med]
Full Article

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Compugen Achieves Second Preclinical Milestone in Cancer Immunotherapy Collaboration with Bayer
Compugen Ltd. disclosed that it has achieved a second milestone in its cancer immunotherapy collaboration it entered last year with Bayer HealthCare. The collaboration provides for the research, development, and commercialization of antibody-based cancer therapeutics against two novel Compugen-discovered immune checkpoint regulators. [Compugen Ltd. (Business Wire)] Press Release

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

Postdoctoral Fellow – Biochemistry (University of Utah)

Postdoctoral Fellow – Cancer Genome Analysis (Ontario Institute for Cancer Research)

Clinical Research Assistant – Diabetes (University of Massachusetts)

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

Research Associate – Bioengineering (Fred Hutchinson Cancer Research Center)

Research Fellow – Molecular and Cellular Cancer Chronotherapeutics Research (The University of Warwick)

Postdoctoral Training Fellow – Systems & Precision Cancer Medicine (Institute of Cancer Research)

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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