Volume 4.18 | May 14

Pancreatic Cell News 4.18 May 14, 2013
     In this issue: Publications | ReviewsIndustry News | Policy News | Events | Jobs 
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TOP STORY
Breakthrough in the Understanding of How Pancreatic Cancer Cells Ingest Nutrients Points to New Drug Target
Researchers have unraveled a longstanding mystery about how pancreatic tumor cells feed themselves, opening up new therapeutic possibilities for a notoriously lethal disease with few treatment options. [Press release from NYU Langone Medical Center discussing online prepublication in Nature]
Press Release | Abstract

Learn More: Column-Free Enrichment of Mouse Mammary Stem & Progenitor Cells
PUBLICATIONS (Ranked by impact factor of the journal)

DIABETES

Adipocyte Lipid Chaperone aP2 Is a Secreted Adipokine Regulating Hepatic Glucose Production
Scientists demonstrated that although established as an intracellular lipid chaperone, aP2 is in fact actively secreted from adipocytes to control liver glucose metabolism. Secretion of aP2 from adipocytes is regulated by fasting- and lipolysis-related signals, and circulating aP2 levels are markedly elevated in mouse and human obesity. [Cell Metab]
Abstract | Graphical Abstract | Press Release

Enhanced Function of Immuno-Isolated Islets in Diabetes Therapy by Co-Encapsulation with an Anti-Inflammatory Drug
Immuno-isolation of islets has the potential to enable the replacement of pancreatic function in diabetic patients. However, host response to the encapsulated islets frequently leads to fibrotic overgrowth with subsequent impairment of the transplanted grafts. Researchers identified and incorporated anti-inflammatory agents into islet-containing microcapsules to address this challenge. [Biomaterials] Abstract

Preventing p38 MAPK-Mediated MafA Degradation Ameliorates β Cell Dysfunction under Oxidative Stress
Researchers previously showed that p38 MAPK, but not GSK3, is a major regulator of MafA degradation under oxidative stress. They examined the mechanisms of this degradation and whether preventing MafA degradation under oxidative stress will overcome β-cell dysfunction. They showed that under oxidative and non-oxidative conditions p38 MAPK directly binds to MafA and triggers MafA degradation via ubiquitin proteasomal pathway. [Mol Endocrinol] Abstract

Reversal of Hyperglycemia by Insulin-Secreting Rat Bone Marrow- and Blastocyst-Derived Hypoblast Stem Cell-Like Cells
β-cell replacement may efficiently cure type 1 diabetic (T1D) patients whose insulin-secreting β-cells have been selectively destroyed by autoantigen-reactive T cells. To generate insulin-secreting cells, researchers used two cell sources: rat multipotent adult progenitor cells (rMAPC) and the highly similar rat extra-embryonic endoderm precursor cells isolated under rMAPC conditions from blastocysts (rHypoSC). rMAPC/rHypoSC were sequentially committed to definitive endoderm, pancreatic endoderm, and β-cell like cells. [PLoS One] Full Article

A Whey Protein Hydrolysate Promotes Insulinotropic Activity in a Clonal Pancreatic β-Cell Line and Enhances Glycemic Function in ob/ob Mice
The effects of a whey protein hydrolysates (WPH) were analyzed in vitro on acute glucose-induced insulin secretion in pancreatic BRIN-BD11 β cells. BRIN-BD11 cells showed a robust and reproducible dose-dependent insulinotropic effect of WPH. [J Nutr] Abstract

Loss of β-Arrestin2 Mediates Pancreatic-Islet Dysfunction in Mice
Investigators found that β-arrestin2 was abundantly expressed in mouse pancreatic beta cells, while its expression was significantly decreased in obese and diabetic mouse models. Hyperglycemic clamp study showed that the first and second phase of insulin secretion were impaired in β-arrestin2 knockout mice. [Biochem Bioph Res Co] Abstract

PANCREATIC CANCER

The Novel c-Met Inhibitor Cabozantinib Overcomes Gemcitabine Resistance and Stem Cell Signaling in Pancreatic Cancer
Investigators evaluated the effect of cabozantinib to stem-like features and therapy resistance. Cabozantinib inhibited viability and spheroid formation and induced apoptosis in malignant cells with minor effects in non-malignant cells. [Cell Death Dis] Full Article

ARID1B, A Member of the Human SWI/SNF Chromatin Remodeling Complex, Exhibits Tumor-Suppressor Activities in Pancreatic Cancer Cell Lines
Researchers have characterized a possible tumor suppressor role for the largest subunit of the SWItch/sucrose nonfermentable (SWI/SNF) complex, namely the AT-rich interaction domain 1B (ARID1B). ARID1B was transcriptionally repressed due to promoter hypermethylation, and ectopic expression severely compromised the ability of MiaPaCa2 cells to form colonies in liquid culture and soft agar. [Brit J Canc] Abstract

Putative Tumor Suppressor Gene SEL1L Was Downregulated by Aberrantly Upregulated hsa-mir-155 in Human Pancreatic Ductal Adenocarcinoma
Scientists investigated whether aberrantly upregulated microRNAs (miRNAs) repressed the expression of SEL1L. From reported miRNA microarray studies on pancreatic ductal adenocarcinoma and predicted miRNA targets, they identified seven aberrantly upregulated miRNAs that potentially target SEL1L. [Mol Carcinogen] Abstract

B7-H4 Enhances Oncogenicity and Inhibits Apoptosis in Pancreatic Cancer Cells
Researchers investigated the mechanisms involved in enhanced oncogenicity and the inhibition of apoptosis by B7-H4 in pancreatic cancer cells. Increased apoptosis in pancreatic cancer cells following B7-H4 silencing was demonstrated in vitro by using flow cytometry and in a xenograft tumor model and was associated with increased caspase activity and decreased Erk1/2 phosphorylation both in vitro and in vivo. [Cell Tissue Res] Abstract

Happy Birthday mTeSR™1! 5 years of Groundbreaking Research and Counting

REVIEWS

Toward a Better Understanding of Pancreatic Ductal Adenocarcinoma: Glimmers of Hope?
This review focuses on pancreatic ductal adenocarcinoma (PDAC) epidemiology and on recent advances in the understanding of the molecular mechanisms of PDAC carcinogenesis. The authors discuss the cancer stem cell hypothesis, which provides a rationale for the pervasive resistance of PDAC to chemoradiotherapy and explains the disease recurrence after the currently used genotoxic treatment. [Pancreas] Abstract

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

INDUSTRY NEWS

Lexicon Advances LX4211 in Type 1 Diabetes Phase II Trial
Lexicon Pharmaceuticals, Inc. announced that it is progressing into the placebo-controlled portion of its Phase II clinical trial of LX4211 in patients with type 1 diabetes, having successfully completed the open-label, pioneer portion of the trial. [Lexicon Pharmaceuticals, Inc.] Press Release

The Market for Pancreatic Cancer Therapies Will Nearly Double to $1.3 Billion in 2022, Fueled by the Entry of Three Novel Agents
Decision Resources finds that the pancreatic cancer therapy market will nearly double to $1.3 billion in 2022, owing to the launch and rapid uptake of three high-priced agents-Celgene/Taiho’s Abraxane, Onconova Therapeutics/Baxter International/SymBio Pharmaceuticals’ Estybon and Merrimack Pharmaceuticals’ MM-398. [Decision Resources, LLC] Press Release

Abbott Announces CE Mark for Test to Aid Doctors with Diagnosing and Monitoring Diabetes
Abbott announced CE Marking (Conformité Européenne) for the ARCHITECT clinical chemistry Hemoglobin A1c test, which may aid physicians in diagnosing and monitoring diabetes as well as identifying patients at risk for developing diabetes. [Abbott Laboratories] 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)

National Health Service (United Kingdom)

Therapeutic Goods Administration (Australia)

EVENTS

NEW International Society for Stem Cell Research
June 12-15, 2013
Boston, United States

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

JOB OPPORTUNITIES

NEW PhD Scholarships - Diabetes (Danish Diabetes Academy)

Postdoctoral Fellow (Johns Hopkins University School of Medicine)


PhD Positions - Molecular Mechanisms Controlling Acinar Cell Proliferation (University Hospital Zuerich)


PhD Studentship - Obesity and Type 2 Diabetes (German Diabetes Center)

Postdoctoral Researcher (The University of Texas Health Science Center at San Antonio)

Scientist/Specialist - Mitochondrial Function (The Nestlé Institute of Health Sciences)

Postdoctoral Position - Pancreatic Cancer (UT Southwestern Medical Center at Dallas)

Postdoctoral Fellow - Pancreatic Beta Cell Regeneration and Survival (Oklahoma Medical Research Foundation)

Research Associate - Progression and Metastasis of Pancreatic and Breast Cancer (University of North Carolina at Charlotte)


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