Pancreatic Cell News Volume 7.37 | Sep 20 2016

TOP STORY

Human Pluripotent Stem Cell-Derived Acinar/Ductal Organoids Generate Human Pancreas upon Orthotopic Transplantation and Allow Disease Modeling

Investigators designed a straightforward approach to direct human pluripotent stem cells towards pancreatic organoids resembling acinar and ductal progeny. [Gut] Full Article

(Ranked by impact factor of the journal)

DIABETES & PANCREATITIS

Adhesion G-Protein Coupled Receptor G1 (ADGRG1/GPR56) and Pancreatic β-Cell Function

The authors showed that the expression of ADGRG1 was reduced in islets of type-2 diabetic donors, in db/db mouse islets and in isolated human islets exposed to chronic hyperglycemia. Beneficial effects of collagen type III on β-cell function via activation of the cAMP/PKA pathway, suppression of RhoA and caspase-3 activity, increased β-cell viability and proliferation were abolished when ADGRG1 was down-regulated in β-cells. [J Clin Endocrinol Metab] Abstract

β-Hairpin of Islet Amyloid Polypeptide Bound to an Aggregation Inhibitor

In type 2 diabetes, the formation of islet amyloid consisting of islet amyloid polypeptide is associated with reduction in β-cell mass and contributes to the failure of islet cell transplantation. The authors characterized a β-hairpin conformation of IAPP in complex with the engineered binding protein β-wrapin HI18. [Sci Rep] Full Article

Endoplasmic Reticulum Stress Links Oxidative Stress to Impaired Pancreatic Beta-Cell Function Caused by Human Oxidized LDL

Reseachers found that human oxidized LDL activates ER stress as evidenced by the activation of the inositol requiring 1α, and the elevated expression of both DDIT3 and DNAJC3 ER stress markers in isolated human islets and the mouse insulin secreting MIN6 cells. [PLoS One] Full Article

PANCREATIC CANCER

Metastatic Progression Is Associated with Dynamic Changes in the Local Microenvironment

Investigators delineate the natural history of metastasis in an autochthonous model of pancreatic ductal adenocarcinoma, using lineage tracing to examine the evolution of disseminated cancer cells and their associated microenvironment. [Nat Commun] Full Article

Genetic Ablation of Smoothened in Pancreatic Fibroblasts Increases Acinar–Ductal Metaplasia

Researchers showed that disruption of paracrine Hedgehog signaling via genetic ablation of Smoothened in stromal fibroblasts in a Kras^G12D mouse model increased acinar-to-ductal metaplasia. [Genes Dev] Abstract

α-Mangostin-Encapsulated PLGA Nanoparticles Inhibit Pancreatic Carcinogenesis by Targeting Cancer Stem Cells in Human, and Transgenic (KrasG12D, and KrasG12D/tp53R270H) Mice

Activation of sonic hedgehog in cancer stem cells (CSC) has been demonstrated with aggressiveness of pancreatic cancer. In order to enhance the biological activity of α-mangostin, scientists formulated mangostin-encapsulated PLGA nanoparticles and examined the molecular mechanisms by which they inhibit human and KC mice pancreatic CSC characteristics in vitro, and pancreatic carcinogenesis in KPC mice. [Sci Rep] Full Article

Dual Oxidase2 and Pancreatic Adenocarcinoma: IFN-γ-Mediated Dual oxidase2 Overexpression Results in H2O2-Induced, ERKassociated Up-Regulation of HIF-1α and VEGF-A

Scientists demonstrated that many human pre-malignant pancreatic intraepithelial neoplasms and frank pancreatic cancers express substantial levels of dual oxidase (DUOX) protein compared to histologically normal pancreatic tissues, and that expression of both DUOX2 and VEGF-A mRNAs is significantly increased in surgically-resected pancreatic cancers compared to the adjacent normal pancreas. [Oncotarget] Full Article

Hes1 Controls Exocrine Cell Plasticity and Restricts Development of Pancreatic Ductal Adenocarcinoma in a Mouse Model

Investigators used a murine genetic in vivo approach to ablate Hes1 in pancreatic progenitor cells. Using this model, they studied the role of Hes1 in both acinar cell plasticity and pancreatic regeneration after caerulein-induced pancreatitis and in Kras,sup>G12D-driven pancreatic ductal adenocarcinoma development. [Am J Pathol] Abstract

C1qTNF Related Protein 4 (CTRP4) Promotes Pancreatic Ductal Adenocarcinoma Cell Proliferation and Migration via Activation of EGFR-PI3K-NF-κB Pathway

Researchers investigated the role of C1qTNF related protein 4 in the progression of pancreatic ductal adenocarcinoma (PDAC). They found that, compared with the adjacent non-cancerous tissues and normal pancreatic cells, CTRP4 was markedly upregulated in human PDAC tissues and cell lines. [Oncol Res] Abstract

MiR-377 Inhibits the Proliferation of Pancreatic Cancer by Targeting Pim-3

Scientists generated pancreatic ductal adenocarcinoma (PDAC) cell lines with stable overexpression or inhibition of miR-377. Their results indicated that miR-377 up-regulation significantly promoted cell viability, proliferation, and migration in PDAC cells, and also induced cell apoptosis and cell cycle arrest simultaneously. [Tumour Biol] Abstract

Role of Sex Steroids in β Cell Function, Growth, and Survival

The author presents a perspective on the physiological roles of estrogens, androgens, and P4 via their receptors in pancreatic β cells in the gender-specific tuning of insulin secretion. He also discusses potential gender-specific therapeutic avenues that this knowledge may open in the future. [Trends Endocrinol Metab] Abstract

Immune and Pancreatic β Cell Interactions in Type 1 Diabetes

The authors explore the various components of the immune response as well as the cellular interactions that are involved in causing or reducing immune damage to the β cells. They consider these in the light of the possibility that understanding them may help identify therapeutic targets to reduce the damage and destruction leading to type 1 diabetes. [Trends Endocrinol Metab] Abstract

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

New-Onset Diabetes May Signal Pancreatic Cancer

Screening adults with new-onset diabetes for pancreatic cancer may be effective for early diagnosis and treatment initiation. [Press release from Endocrine Today discussing research presented at The 52^nd European Association for the Study of Diabetes Annual Meeting, Munich] Press Release

Semma Therapeutics Announces $5 Million Grant from California Institute of Regenerative Medicine (CIRM) to Develop Novel Stem-Cell Derived Treatment for Diabetes

Semma Therapeutics announced that it has accepted a $5 million grant from the California Institute of Regenerative Medicine. The award provides funding to develop personalized cell therapy for the treatment of diabetes. Diabetic patients’ own cells will be collected, transformed first into stem cells and then differentiated into stem-cell derived pancreatic islets to use as an investigational cell therapy for diabetes. [Semma Therapeutics] Press Release

CivaTech Oncology Inc. Awarded up to $2.3M from NIH for Pancreatic Cancer Study with CivaSheet^® Device

CivaTech Oncology Inc. has received a notice of award from the NIH NCI SBIR Fast Track program for the first Phase of an 80 patient, multi-center pancreatic cancer study with the new FDA cleared CivaSheet^® device. [CivaTech Oncology Inc. (BusinessWire)] Press Release

BioLineRx Announces Initiation of Phase IIa Trial of BL-8040 in Combination with KEYTRUDA^® for Treatment of Pancreatic Cancer

BioLineRx Ltd. announced the initiation of a Phase IIa trial investigating BL-8040 in combination with KEYTRUDA^®, MSD’s anti-PD-1 therapy, in patients with metastatic pancreatic cancer. [BioLineRx Ltd.] Press Release

Eleven Medicines Recommended for Approval, Including Three Medicines for Cancer

The European Medicines Agency’s Committee for Medicinal Products for Human Use recommended eleven medicines for approval at its September meeting. [The European Medicines Agency] Editorial

University of Tokyo to Investigate Data Manipulation Charges Against Six Prominent Research Groups

The University of Tokyo announced it is launching an investigation into anonymously made claims of fabricated and falsified data appearing in 22 papers by six university research groups. [Science Insider] Editorial

NEW The Second International Conference on Diabetes Mellitus
December 1-3, 2016
Sanya, China

NEW The Second International Conference on Gastroenterology and Hepatology (ICGEH 2016)
December 1-3, 2016
Sanya, China

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

NEW Vice President – Pancreatic Cancer Disease Lead (Celgene Corporation)

NEW Postdoctoral Research Fellow – Pancreas Cancer (Fred Hutchinson Cancer Research Center)

NEW Postdoctoral Fellowship- Pacreatic Islet Biology (University of Michigan Medical School)

Chair of Medical Biology (Masaryk University)

Postdoctoral Position – Cancer Research (Sanford Burnham Prebys Medical Discovery Institute)

Assistant Scientist – Diabetes Research (University of Miami)

Postdoctoral Fellow – Pancreatic Biology (Toronto General Research Institute & McEwen Centre for Regenerative Medicine)

Vice President – Legacy Research Institute (Legacy Health)

Postdoctoral Fellow – Pancreatic Stem Cell Biology (University of Southern California)

Research Histotechnologist I (Fred Hutchinson Cancer Research Center)

Recruit Top Talent: Reach 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? Submit your feedback here.