Pancreatic Cell News Volume 4.21 | Jun 4 2013

The Cancer-Associated FGFR4-G388R Polymorphism Enhances Pancreatic Insulin Secretion and Modifies the Risk of Diabetes
Scientists showed that the fibroblast growth factor receptor 4 (FGFR4)-R388 allele yields a receptor variant that preferentially promotes STAT3/5 signaling. This STAT activation transcriptionally induces Grb14 in pancreatic endocrine cells to promote insulin secretion. [Cell Metab] Abstract

DIABETES

Innate Pro-B-Cell Progenitors Protect against Type 1 Diabetes by Regulating Autoimmune Effector T Cells
Researchers provide evidence for innate pro-B-cell progenitor (pro-B) cells that emerged within the bone marrow both in vitro and in vivo upon Toll-like receptor-9 activation and whose adoptive transfer protected nonobese diabetic mice against type 1 diabetes. [Proc Natl Acad Sci USA] Abstract

Protection of Islet Grafts through TGF Beta Induced Tolerogenic DC
Scientists investigated the possibilities of transient expression of the immunosuppressive cytokine Transforming Growth Factor (TGF) beta within islets to achieve long term graft tolerance. They found that brief expression of TGF beta prevented rejection of syngeneic islets, that there was reduction of dendritic cell activation in the graft and reduced reactivation of T cells in the graft draining lymph nodes. [Diabetes] Abstract

Recovery from Overt Type 1 Diabetes Ensues When Immune Tolerance and β Cell Formation Are Coupled with Regeneration of Endothelial Cells in the Pancreatic Islets
Scientists have previously shown that Ig-GAD2, carrying glutamic acid decarboxylase (GAD) 206-220 peptide, induced in hyperglycemic mice immune modulation that was able to control pancreatic inflammation, stimulate β-cell regeneration and prevent type 1 diabetes (T1D) progression. Herein, they showed that the same Ig-GAD2 regimen given to mice with overt T1D is unable to reverse the course of disease despite eradication of Th1 and Th17 cells from the pancreas. [Diabetes] Abstract | Press Release

Specification of Hepatopancreas Progenitors in Zebrafish by hnf1ba and wnt2bb
Using a novel hypomorphic hnf1ba zebrafish mutant that exhibits pancreas hypoplasia, as observed in HNF1B monogenic diabetes, scientists showed that hnf1ba plays essential roles in regulating β-cell number and pancreas specification, distinct from its function in regulating pancreas size and liver specification, respectively. [Development] Abstract

Electrofusion of Mesenchymal Stem Cells and Islet Cells for Diabetes Therapy: A Rat Model
The authors hypothesized that electrofusion between mesenchymal stem cells (MSC) and islet cells may yield robust islet cells for diabetes therapy. They established a method of electrofusion between dispersed islet cells and MSCs in rats. The fusion cells maintained glucose-responsive insulin release for 20 days in vitro. [PLoS One] Full Article

A Short-Activating RNA Oligonucleotide Targeting the Islet β-Cell Transcriptional Factor MafA in CD34⁺ Cells
Researchers have developed a novel approach using short-activating RNA oligonucleotides to differentiate adult human CD34⁺ cells into insulin-secreting cells. By transfecting RNA to increase transcript levels of the master regulator of insulin biosynthesis, v-maf musculoaponeurotic fibrosarcoma oncogene homolog A (MafA), several pancreatic endodermal genes were upregulated during the differentiation procedure. [Mol Ther Nucleic Acids] Full Article

PANCREATIC CANCER

Extracellular DNA in Pancreatic Cancer Promotes Cell Invasion and Metastasis
Investigators report that extracellular DNA (exDNA) is present on the surface of pancreatic cancer cells where it is critical for driving metastatic behavior. ExDNA was abundant on the surface and vicinity of cultured pancreatic cancer cells, but absent from normal pancreas cells. [Cancer Res] Abstract | Full Article

MicroRNA Array Analysis Finds Elevated Serum miR-1290 Accurately Distinguishes Patients with Low-Stage Pancreatic Cancer from Healthy and Disease Controls
Researchers measured 735 microRNAs (miRNAs) in pancreatic cancer case and control sera by QRTPCR using TaqMan® MicroRNA Arrays. After array analysis, they selected 18 miRNA candidates for validation in an independent set of cases and control samples. miR-1290 influenced in vitro pancreatic cancer cell proliferation and invasive ability. [Clin Cancer Res] Abstract

Suppression of Pancreatic Tumor Growth by Targeted Arsenic Delivery with Anti-CD44v6 Single Chain Antibody Conjugated Nanoparticles
A maleimide-functionalized amphiphilic diblock copolymer of poly (ethylene glycol) and poly (d, l-lactide) (mal-PEG-PDLLA) was synthesized and assembled to vesicles with arsenite ion (As) encapsulated in their cores. Conjugation of scFv_CD44v6 with mal-PEG-PDLLA enabled more efficient delivery of As and exhibited higher cytotoxic activity than non-targeted ones in human pancreatic cancer cells PANC-1. [Biomaterials] Abstract

MLH1 As a Direct Target of miR-155 and a Potential Predictor of Favorable Prognosis in Pancreatic Cancer
MicroRNA (miR)-155 mimics and inhibitor were transfected to pancreatic cancer cell lines, Panc-1 and Capan-1. Expression of Mut L homologue 1 (MLH1) was subsequently evaluated. Transfection of miR-155 mimics and inhibitor led to reversely altered protein expressions of miR-155 and MLH1, whereas the corresponding mRNA expressions were similar. [J Gastrointest Surg] Abstract

SDF-1α Upregulation of MMP-2 Is Mediated by p38 MAPK Signaling in Pancreatic Cancer Cell Lines
Analysis of stromal cell-derived factor-1α (SDF-1α), CXC chemokine receptor-4 and MMP-2 expression in pancreatic cancer and adjacent tissue samples from ten patients revealed that all three proteins are overexpressed in human pancreatic cancer. SDF-1α induced MMP-2 and MMP-9 upregulation in PANC-1 and SW-1990 cells, which was associated with increased pancreatic cancer cell proliferation and invasion. [Mol Biol Rep] Abstract

REVIEWS

How to Make a Functional β-Cell
Recent insights into β-cell development, combined with the discovery of pluripotent stem cells, have led to an unprecedented opportunity to generate new β-cells for transplantation therapy and drug screening. Progress has also been made in converting terminally differentiated cell types into β-cells using transcriptional regulators identified as key players in normal development, and in identifying conditions that induce β-cell replication in vivo and in vitro. [Development] Full Article

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

Analyses of MPACT Trial Evaluating ABRAXANE® Combination Therapy for the Treatment of Advanced Pancreatic Cancer Presented at ASCO 2013
Celgene International Sàrl, a subsidiary of Celgene Corporation, announced several analyses of a phase III clinical trial of ABRAXANE^® in combination with gemcitabine in previously untreated patients with advanced pancreatic cancer. [Press release from Celgene International Sàrl discussing research presented at the American Society of Clinical Oncology (ASCO) 2013 Annual Meeting, Chicago] Press Release

NewLink Genetics’ Algenpantucel-L Shows Encouraging Disease-Free and Overall Survival in Phase II Study in Resected Pancreatic Cancer
NewLink Genetics Corporation announced results from a Phase II clinical study with its drug candidate algenpantucel-L. The open-label, two-armed, multi-center study evaluated algenpantucel-L plus standard-of-care adjuvant therapy in 69 patients with resected pancreatic cancer. [Press release from NewLink Genetics Corporation discussing research presented at the American Society of Clinical Oncology (ASCO) 2013 Annual Meeting, Chicago] Press Release

From our sponsor:
Looking for ALDH⁺ cancer stem cells? Watch a video to see how ALDEFLUOR^TM can help.

MannKind Completes Phase III Clinical Study of AFREZZA in Patients with Type 1 Diabetes
MannKind Corporation announced that all follow-up visits have been completed for the patients enrolled in Study 171, a Phase III clinical study of AFREZZA^® (insulin human [rDNA origin]) inhalation powder, an investigational, ultra rapid-acting mealtime insulin therapy, administered using MannKind’s next-generation inhaler. [MannKind Corporation] Press Release

New Alliance for European Excellence and Competitiveness in Life Sciences
At the Centre for Genomic Regulation, in Barcelona, directors and staff from ten top European research institutes will kick off a new alliance, called EU-LIFE, that will promote European research. The mission of EU-LIFE is to foster excellence, share knowledge, and influence policies in life sciences. [VIB] Press Release

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)

NEW 14th International TNF Conference: Tumor Necrosis Factor 2013
July 7-10, 2013
Quebec City, Canada

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

NEW Diabetes UK PhD Studentship (Diabetes UK)

Postdoctoral Fellow – Beta Cell Biology (Sanford Research/University of South Dakota)

PhD Scholarships – Diabetes (Danish Diabetes Academy)

Postdoctoral Fellow – Stem Cell and Cancer Biology (Johns Hopkins University School of Medicine)

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

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

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

Recruit Top Talent: Reach more than 50,000 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? Email info@connexoncreative.com with your feedback.