Pancreatic Cell News Volume 9.00 | Jan 2 2018

TOP STORY

β2 Adrenergic-Neurotrophin Feedforward Loop Promotes Pancreatic Cancer

Pancreatic Ngf overexpression accelerated tumor development in LSL-Kras^+/G12D;Pdx1-Cre mice. ADRB2 blockade together with gemcitabine reduced nerve growth factor expression and nerve density, and increased survival of LSL-Kras^+/G12D;LSL-Trp53^+/R172H;Pdx1-Cre mice. [Cancer Cell] Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

DIABETES & PANCREATITIS

SRp55 Regulates a Splicing Network that Controls Human Pancreatic Beta Cell Function and Survival

Researchers showed that SRp55, a splicing factor regulated by the diabetes susceptibility gene GLIS3, has a major role in maintaining function and survival of human beta cells. [Diabetes] Abstract

A Targeted RNAi Screen Identifies Endocytic Trafficking Factors that Control GLP-1 Receptor Signaling in Pancreatic Beta Cells

Investigators screened 29 proteins with known functions in G protein-coupled receptor trafficking for their role in GLP-1R potentiation of insulin secretion in pancreatic beta cells. [Diabetes] Abstract

MiR-184 Expression Is Regulated by AMPK in Pancreatic Islets

Researchers explored the miRNAs acting downstream of AMPK in mouse and human β-cells. They identified 14 down-regulated and 9 up-regulated miRNAs in βAMPKdKO vs. control islets. [FASEB J] Abstract

Microphysiological Analysis Platform of Pancreatic Islet β-Cell Spheroids

The authors reported a microphysiological analysis platform that allows the uniform 3D spheroid formation of pancreatic β-cell islets, large-scale morphological phenotyping, and gene expression mapping of chronic glycemia and lipidemia development. [Adv Healthc Mater] Abstract

Purification of Replicating Pancreatic β-Cells for Gene Expression Studies

To study the replication-related β-cell biology, scientists designed a replicating β-cells sorting system for gene expression experiments. Replicating β-cells were identified by EdU incorporation and purified by flow cytometry. [Sci Rep] Full Article

PANCREATIC CANCER

Loss of PTEN and Activation of Kras Synergistically Induce Formation of Intraductal Papillary Mucinous Neoplasia from Pancreatic Ductal Cells in Mice

Investigators identified cells that form intraductal papillary mucinous neoplasias (IPMNs) and mutations that promote IPMN development and progression. [Gastroenterology] Abstract

Krüppel-like Factor 5, Increased in Pancreatic Ductal Adenocarcinoma, Promotes Proliferation, Acinar to Ductal Metaplasia, Pancreatic Intraepithelial Neoplasia, and Tumor Growth in Mice

Researchers investigated the role of the transcription factor Krüppel-like factor 5 in acinar to ductal metaplasia and KRAS-mediated formation of pancreatic intraepithelial neoplasia. [Gastroenterology] Abstract

Amphiphilic Nanocarrier-Induced Modulation of PLK1 and miR-34a Leads to Improved Therapeutic Response in Pancreatic Cancer

The authors showed a potent combination of microRNA and siRNA delivered by an efficient nanocarrier to pancreatic ductal adenocarcinoma (PDAC) tumors. Using proteomic-microRNA profiles and survival data of PDAC patients from TCGA, they found a novel signature for prolonged survival. [Nat Commun] Full Article | Press Release

Adaptive and Reversible Resistance to Kras Inhibition in Pancreatic Cancer Cells

Investigators analyzed the requirement of endogenous Kras to maintain survival of murine pancreatic ductal adenocarcinoma cells, using an inducible shRNA-based system that enables temporal control of Kras expression. [Cancer Res] Abstract | Full Article

Precision Design of Nanomedicines to Restore Gemcitabine Chemosensitivity for Personalized Pancreatic Ductal Adenocarcinoma Treatment

Low chemosensitivity considerably restricts the therapeutic efficacy of gemcitabine (GEM) in pancreatic cancer treatment. Scientists found that decreased expression of human equilibrative nucleoside transporter-1 and increased expression of ribonucleotide reductase subunit 2 was associated with low GEM chemosensitivity. [Biomaterials] Abstract

Demethylzeylasteral (ZST93) Inhibits Cell Growth and Enhances Cell Chemosensitivity to Gemcitabine in Human Pancreatic Cancer Cells via Apoptotic and Autophagic Pathways

Scientists assessed the effects of ZST93 on cell proliferation and its role in the chemosensitivity to gemcitabine in human pancreatic cancer cells. [Int J Cancer] Abstract

mTORC1 Signaling: A Double-Edged Sword in Diabetic β Cells

While numerous in vitro and in vivo studies reported the positive functions of mechanistic target of rapamycin complex 1 (mTORC1) in the regulation of β cell survival and proliferation under physiological conditions, more recent work demonstrates the opposite in the long term; this is exemplified by the constitutive inappropriate hyper-activation of mTORC1 in diabetic islets or β cells under conditions of increased β cell stress and metabolic demands. [Cell Metab] Abstract

AMPK and Friends: Central Regulators of β Cell Biology

Recent data have shown that both insulin secretion and β cell mass dynamics are regulated by the liver kinase B1-AMP-activated kinase (LKB1-AMPK) pathway and related kinases of the AMPK family; thus, an improved understanding of the biological roles of AMPK in the β cell is now of considerable interest. [Trends Endocrinol Metab] Abstract

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

MabVax Therapeutics Announces Completion of Enrollment and Initial Patient Dosing in an Expanded Cohort of the Phase I Trial Evaluating MVT-5873 in Combination with First-Line Chemotherapy

MabVax Therapeutics Holdings, Inc. announced the completion of enrollment and initial patient dosing in an expanded cohort of the company’s Phase I trial evaluating MVT-5873 in combination with standard of care chemotherapy in newly diagnosed patients with pancreatic and other CA19-9 positive malignancies. [MabVax Therapeutics Holdings, Inc.] Press Release

Completion of Enrollment and Dosing in Initial Cohort of MVT-1075 Radioimmunotherapy Phase I Trial for the Treatment of Pancreatic, Colon and Lung Cancers

MabVax Therapeutics Holdings, Inc. announced the completion of enrollment and dosing of all patients in the initial cohort of the Phase I clinical trial evaluating the company’s new human antibody-based radioimmunotherapy product MVT-1075 for the treatment of pancreatic, colon and lung cancer. [MabVax Therapeutics Holdings, Inc.] Press Release

FDA Approves SGLT2 Inhibitor STEGLATRO^™ (Ertugliflozin) and Fixed-Dose Combination STEGLUJAN^™ (Ertugliflozin and Sitagliptin) for Adults with Type 2 Diabetes

Merck and Pfizer Inc. announced that the FDA has approved STEGLATRO^™ tablets, an oral sodium-glucose cotransporter 2 (SGLT2) inhibitor, and the fixed-dose combination STEGLUJAN^™ tablets. [Merck Sharp & Dohme Corp.] Press Release

Novocure Receives FDA IDE Approval for its PANOVA 3 Phase III Pivotal Clinical Trial in Advanced Pancreatic Cancer

Novocure announced that it has received FDA Investigational Device Exemption (IDE) approval to initiate its PANOVA 3 clinical trial. The randomized Phase III pivotal trial is designed to determine the efficacy and safety of tumor treating fields with nab-paclitaxel and gemcitabine as a front-line treatment for unresectable locally advanced pancreatic cancer. [Novocure] Press Release

New NCI Director Expects Big Data to Revolutionize Cancer Research, Care

Cancer researchers were nervous early this year about who President Donald Trump would choose to replace Harold Varmus as director of the National Cancer Institute (NCI). But their fears of an unconventional candidate proved unfounded when he tapped Norman “Ned” Sharpless. Sharpless, 51, who was then director of the Lineberger Comprehensive Cancer Center at the University of North Carolina in Chapel Hill [ScienceInsider] Editorial

Nobel Laureate Will Step Down from Leading Embattled Salk Institute

Elizabeth Blackburn, the Nobel Prize–winning molecular biologist who took over just 2 years ago as president of the Salk Institute for Biological Studies in San Diego, California, announced her intent to retire next summer. The unexpected news comes as Salk faces gender discrimination lawsuits from three veteran female scientists and Blackburn herself has been challenged for not moving quickly enough to change what one plaintiff’s suit called an “old boys club” at the renowned research institute. [ScienceInsider] Editorial

Chile Election Reignites Tussle over Science Policy

Chile’s new President-elect Sebastián Piñera is poised to reshape science policy in the country. His plans to forge closer ties among science, education and industry have sparked enthusiasm from scientists who hope the plan will bolster support for their work — but also concern about possible changes in research priorities. [Nature News] Editorial

Facebook Billionaire Pours Funds into High-Risk Research

After his plan to test a cancer vaccine for middle-aged pet dogs was rejected by the US National Institutes of Health, inventor and biochemist Stephen Johnston sought funding outside the mainstream system. The Open Philanthropy Project, a grant-giving organization that is largely funded by Facebook co-founder Dustin Moskovitz and his wife Cari Tuna, announced that Johnston will receive US$6.4 million to test the vaccine he developed. [Nature News] Editorial

NEW 11^th Dutch Stem Cell Meeting
May 4, 2018
Utrecht, Netherlands

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

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

NEW Postdoctoral Research Fellow – Structure-Guided Drug Discovery (Univertsity of Hertfordshire)

NEW Postdoctoral Fellow – Diabetes (Icahn School of Medicine at Mount Sinai)

Research Technologist – Pancreatic Cell Biology (STEMCELL Technologies Inc.)

PhD Studentship – Pancreatic Cancer (CRUK Manchester Institute)

Postdoctoral Fellowship – Pancreatic Cancer (Memorial Sloan Kettering Cancer Center)

PhD Studentship – Pancreas Development and Stem Cells (Helmholtz Zentrum München)

Postdoctoral Positions – Pancreatic Cancer (MD Anderson Cancer Center)

Scientist – Diabetes and Obesity (Helmholtz Zentrum München)

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