Volume 4.48 | Dec 10

Pancreatic Cell News 4.48 December 10, 2013
Pancreatic Cell News
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p53 Status Determines the Role of Autophagy in Pancreatic Tumor Development
Researchers showed, in a humanized genetically-modified mouse model of pancreatic ductal adenocarcinoma, that autophagy’s role in tumor development is intrinsically connected to the status of the tumor suppressor p53. [Nature] Abstract
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PUBLICATIONS (Ranked by impact factor of the journal)

Role of KATP Channels in Glucose-Regulated Glucagon Secretion and Impaired Counterregulation in Type 2 Diabetes
Investigators showed that α cell KATP-channel activity is very low under hypoglycemic conditions and that hyperglycemia, via elevated intracellular ATP/ADP, leads to complete inhibition. [Cell Metab]
Full Article | Graphical Abstract

Long-Term IKK2/NF-κB Signaling in Pancreatic β-Cells Induces Immune-Mediated Diabetes Mellitus
To investigate the potential diabetogenic effects of NF-κB in β-cells, scientists generated a gain-of-function model allowing conditional IKK2/NF-κB activation in β-cells. [Diabetes] Abstract

Identification and Characterization of Glucagon-Like Peptide-1 Receptor Expressing Cells Using a New Transgenic Mouse Model
Using newly-generated glp1r-cre mice crossed with fluorescent reporter strains, researchers showed that major sites of glucagon-like peptide-1 receptor glp1r expression include pancreatic β and δ-cells, vascular smooth muscle, cardiac atrium, gastric antrum/pylorus, enteric neurons and vagal and dorsal root ganglia. [Diabetes] Abstract

Ectopic Ptf1a Expression in Murine ESCs Potentiates Endocrine Differentiation and Models Pancreas Development In Vitro
Scientists derived and characterized a mouse embryonic stem cells (ESCs) line with tetracycline-inducible expression of pancreas-specific transcription factor 1a (PTF1a). They found that transient ectopic expression of PTF1a initiated the pancreatic program in differentiating ESCs causing cells to activate pancreatic duodenal homeobox 1 expression in bud-like structures resembling pancreatic primordia in vivo. [Stem Cells] Abstract

Rhein, a Natural Anthraquinone Derivative, Attenuates the Activation of Pancreatic Stellate Cells and Ameliorates Pancreatic Fibrosis in Mice with Experimental Chronic Pancreatitis
In cultured pancreatic stellate cells, researchers demonstrated that the expression levels of transforming growth factor-beta-stimulated fibrogenic markers including alpha-smooth muscle actin, fibronectin 1 and type I collagen as well as sonic hedgehog were all notably suppressed by the application of rhein at 10 μM. [PLoS One] Full Article


Role of CYB5A in Pancreatic Cancer Prognosis and Autophagy Modulation
The role of CYB5A was tested in 11 pancreatic ductal adenocarcinoma cell lines and five primary cultures through retrovirus-mediated upregulation and small interfering RNA using wound-healing, invasion, annexin-V, electron microscopy, and autophagic assays, as well as autophagy genes and kinases arrays. [J Natl Cancer Inst] Abstract

Mapk Signaling Is Required for Dedifferentiation of Acinar Cells and Development of Pancreatic Intraepithelial Neoplasia in Mice
Scientists investigated whether mitogen-activated protein kinase (Mapk) signaling is required for the initiation and maintenance of pancreatic carcinogenesis in mice. In inducible-KrasG12D and p48Cre mice, Mapk signaling is required for the initiation and maintenance of pancreatic cancer precursor lesions. [Gastroenterology] Abstract

Mutant KRAS Is a Druggable Target for Pancreatic Cancer
Treatment of pancreatic ductal adenocarcinoma cells with siG12D Local Drug EluteR (LODER) resulted in a significant decrease in KRAS levels, leading to inhibition of proliferation and epithelial-mesenchymal transition. [Proc Natl Acad Sci USA] Abstract

Hypoxia-Independent Gene Expression Mediated by Sox9 Promotes Aggressive Pancreatic Tumor Biology
Transcriptomic profiles were compared between the non-metastatic pancreatic cancer cell line FG and its angiogenic/metastatic derivate L3.6pl under normoxic or hypoxic conditions. Cluster analysis revealed a number of transcripts that were induced by hypoxia in non-metastatic cancer cells. [Mol Cancer Res] Abstract

Role of the Hypoxia-Inducible Factor-1 Alpha Induced Autophagy in the Conversion of Non-Stem Pancreatic Cancer Cells into CD133+ Pancreatic Cancer Stem-Like Cells
Recently, several researchers proposed that non-stem cancer cells can convert to stem-like cells to maintain equilibrium. The present study focuses on whether non-stem pancreatic cancer cells can convert to stem-like cells and the role of HIF-1alpha and autophagy in modulating this conversation. [Cancer Cell Int]
Abstract | Full Article

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Role of Adenosine Signaling and Metabolism in β-Cell Regeneration
In this review, both intracellular and extracellular mechanisms of adenosine and ATP are discussed in terms of their established and putative effects on β-cell regeneration. [Exp Cell Res] Abstract

Visit our reviews page to see a complete list of reviews in the pancreatic cell research field.
Melior Licenses Novel Diabetes Drug to Bukwang Pharmaceutical Co.
Melior Pharmaceuticals I, Inc. announced a licensing agreement with Bukwang Pharmaceutical Co. Ltd. to develop, manufacture and commercialize its lead compound MLR-1023, a first-in-class insulin sensitizer for the treatment of type 2 diabetes. [Melior Pharmaceuticals I, Inc.] Press Release

3-V Biosciences Commences Patient Dosing in Phase I Clinical Study of FASN Inhibitor TVB-2640 in Patients with Advanced Solid Tumors
3-V Biosciences, Inc. announced the recent initiation of a Phase I clinical study of TVB-2640 in patients with advanced solid tumors. In a series of preclinical studies, 3-V’s fatty acid synthase (FASN) inhibitors demonstrated potent activity against multiple tumor types, including breast, lung, pancreatic, ovarian and colon cancers. [3-V Biosciences, Inc.] Press Release

Holiday Rock & Roll Bash Breaks All-Time Record: More than $1.95 Million Raised to Benefit the Lustgarten Foundation for Pancreatic Cancer Research
Cablevision Systems Corporation, AMC Networks, and The Madison Square Garden Company hosted the thirteenth annual Holiday Rock & Roll Bash to benefit The Lustgarten Foundation, the nation’s largest nonprofit funder of pancreatic cancer research. Held at the Hard Rock Cafe in New York City, the event raised more than $1.95 million. [The Lustgarten Foundation and CSC Holdings, LLC] Press Release

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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)
NEW Excellence in Diabetes Conference 2014
February 28 – March 2, 2014
Doha, Qatar

Visit our events page to see a complete list of events in the pancreatic cell community.
NEW Postdoctoral Research Associate – Tumor Microenvironment in Pancreatic Cancer Progression (University of Liverpool)

Clinical MD – Clinical Development Program for Oncology and Autoimmune Diseases (Immunomedics, Inc.)

Chief Medical Officer – Novel Therapeutics in Oncology and Autoimmune Disease (Immunomedics, Inc.)

Physician – Diabetes Clinical Research (Eli Lilly)

Postdoctoral Fellowship – Novel Beta Cell Biomarkers (Université Libre de Bruxelles)

Cancer Research UK Cambridge Institute PhD Studentships (University of Cambridge)

Faculty Fellowship – Diabetes Research (Joslin Diabetes Center)

Postdoctoral Position – Pancreatic Cancer Research (The University of Texas Health Science Center at San Antonio)

Faculty Position – Department of Cellular & Structural Biology (The University of Texas Health Science Center at San Antonio)

Scientist – Particle Chemistry (STEMCELL Technologies Inc.)

Research Technologist – Human Pluripotent Stem Cell Products (STEMCELL Technologies Inc.)

Research Associate/Scientist – Antibodies Group (STEMCELL Technologies Inc.)

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