Pancreatic Cell News Volume 10.41 | Oct 22 2019

TOP STORY

A Novel KDM5A/MPC-1 Signaling Pathway Promotes Pancreatic Cancer Progression via Redirecting Mitochondrial Pyruvate Metabolism

TCGA database, paired PDA and adjacent normal pancreatic tissues, PDA tissue array and cell lines were used to determine the levels of mitochondrial pyruvate carrier 1 and KDM5A expression, and their relationship with the clinicopathologic characteristics and overall survival of PDA patients. [Oncogene] Abstract

(Ranked by impact factor of the journal)

DIABETES & PANCREATITIS

Novel Mitochondrial Transition Pore Inhibitor N-Methyl-4-Isoleucine Cyclosporin Is a New Therapeutic Option in Acute Pancreatitis

Pancreatic ductal and acinar cells were isolated by enzymatic digestion from Bl/6 mice. In vitro measurements were performed by confocal microscopy and microfluorometry. Preventive effects of pharmacological or genetic inhibition of the mitochondrial transition pore during the administration of either bile acids or ethanol and fatty acids were examined. [J Physiol] Abstract

SOX9⁺/PTF1A⁺ Cells Define the Tip Progenitor Cells of the Human Fetal Pancreas of the Second Trimester

The authors investigated the tip progenitor domain in the branched epithelium of human fetal pancreas between 13.5 and 17.5 gestational weeks by immunohistological staining. They also used a novel RNA-based technology to isolate live cells followed by gene expression analyses. They identified cells co-expressing SOX9 and PTF1A, two transcription factors known to be important for pancreatic multipotent progenitor cells, within the tips of the epithelium and observed a decrease in their proportions over time. [Stem Cells Transl Med] Full Article

PANCREATIC CANCER

SPOP Suppresses Pancreatic Cancer Progression by Promoting the Degradation of NANOG

Analysis of patient tissues showed decreased speckle-type POZ domain protein (SPOP) expression, which was associated with poor prognosis. SPOP knockdown in SW1990 (in vitro/vivo) and PANC-1 (in vitro) cells led to significantly greater proliferation, migration, and invasion. [Cell Death Dis] Full Article

YY1 Targets Tubulin Polymerisation-Promoting Protein to Inhibit Migration, Invasion and Angiogenesis in Pancreatic Cancer via p38/MAPK and PI3K/AKT Pathways

Scientists performed ChIP-sequencing and found that Yin Yang 1 (YY1) directly bound to the promoter region of tubulin polymerisation-promoting protein (TPPP). The expression of TPPP in pancreatic cancer was detected by western blotting and immunohistochemistry. [Br J Cancer] Abstract

YAP Inhibition by Nuciferine via AMPK-Mediated Downregulation of HMGCR Sensitizes Pancreatic Cancer Cells to Gemcitabine

Researchers showed that nuciferine could enhance the sensitivity of pancreatic cancer cells to gemcitabine in both cultured cells and the xenograft mouse model. The mechanism study demonstrated that nuciferine induced YAP Ser127 phosphorylation through AMPK-mediated 3-hydroxy-3-methyl-glutaryl-coA reductase (HMGCR) downregulation. [Biomolecules] Full Article

Ealamines A–H, a Series of Naphthylisoquinolines with the Rare 7,8′-Coupling Site, from the Congolese Liana Ancistrocladus ealaensis, Targeting Pancreatic Cancer Cells

Ealamines A–D exhibited distinct—and specific—antiplasmodial activities, and they displayed pronounced preferential cytotoxic effects toward PANC-1 human pancreatic cancer cells in nutrient-deprived medium, without causing toxicity under normal, nutrient-rich conditions, with ealamine C as the most potent agent. [J Nat Prod] Abstract

Impact of CD36 on Chemoresistance in Pancreatic Ductal Adenocarcinoma

CD36 expression was characterized using immunohistochemistry in 95 clinical specimens resected from patients with pancreatic ductal adenocarcinoma (PDAC). They divided patients into two groups, with different CD36 expression levels, and analyzed and compared their prognoses. CD36 expression was also assessed in PDAC cell lines. [Ann Surg Oncol] Abstract

Differential Secretome of Pancreatic Cancer Cells in Serum-Containing Conditioned Medium Reveals CCT8 as a New Biomarker of Pancreatic Cancer Invasion and Metastasis

Investigators used a pair of homologous pancreatic cancer cell supernatants with different capacities for invasion and metastasis to examine secreted proteins in the conditioned media without the removal of fetal bovine serum, namely through size exclusion chromatography combined with high-abundance protein affinity chromatography to enrich low-concentration protein, followed by mass spectrometry using triple dimethyl labeling. [Cancer Cell Int] Full Article

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CAF Subpopulations: A New Reservoir of Stromal Targets in Pancreatic Cancer

The authors explore how different aspects of cancer-associated fibroblasts (CAF) heterogeneity are defined and how these manifest in multiple cancers, with a focus on pancreatic ductal adenocarcinoma (PDAC). They also discuss therapeutic approaches to selectively target protumourigenic CAF functions, while avoiding normal fibroblasts, providing insight into the future of stromal targeting for the treatment of PDAC and other solid tumors. [Trends Cancer] Abstract

Recent Insights Into Mechanisms of β-Cell Lipo- and Glucolipotoxicity in Type 2 Diabetes

Investigators review the current evidence supporting the role of pancreatic β-cell lipo- and glucolipotoxicity in type 2 diabetes, including lipid-based interventions in humans, prospective epidemiological studies and human genetic findings. In addition to total free fatty acids (FFA) quantity, the quality of FFA is a key determinant of lipotoxicity. [J Mol Biol] Abstract | Graphical Abstract

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PharmaCyte Biotech Successfully Completes Manufacturing of Clinical Trial Product

PharmaCyte Biotech, Inc. announced that its partner, Austrianova Singapore, has completed the first of two staggered and back to back manufacturing runs for the production of PharmaCyte’s clinical trial product. The clinical trial product will be used in PharmaCyte’s clinical trial in locally advanced, inoperable pancreatic cancer. [PharmaCyte Biotech, Inc.] Press Release

Lilly Announces Phase III Study in Patients With Metastatic Pancreatic Cancer Did Not Meet Primary Endpoint of Overall Survival

Eli Lilly and Company announced top-line results from its Phase III SEQUOIA trial evaluating pegilodecakin plus FOLFOX compared to FOLFOX alone in patients with metastatic pancreatic cancer whose disease had progressed during or following a first-line gemcitabine–ontaining regimen. The SEQUOIA trial did not meet its primary endpoint of overall survival. [Eli Lilly and Company] Press Release

Female Researchers in Australia Less Likely to Win Major Medical Grants than Males

Female scientists in Australia were less likely to win a major type of medical-research grants this year than their male counterparts, despite an overhaul of the country’s science funding that was supposed to address gender inequity. [Nature News] Editorial

Trump Names Seven to Revived Presidential Science Advisory Panel

Thirty-three months after taking office, President Donald Trump has chosen a group of business leaders to advise him on science and technology policy. [ScienceInsider] Editorial

UK Science Minister Says DARPA-Like Agency Is in the Works

The UK government is working to establish a “blue sky” funding agency similar to the US Defense Advanced Research Projects Agency, UK science minister Chris Skidmore told the Science and Technology Select Committee of Parliament’s House of Commons. [ScienceInsider] Editorial

NEW Tumor Immunology and Immunotherapy
November 17-20, 2019
Boston, Massachusetts, United States

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NEW Studentship – Hormone Secretion in Islet Cells (Uppsala University)

Research Associate – Human Organogenesis (The University of Manchester)

Group Leader – Diabetes Research (International Centre for Genetic Engineering and Biotechnology)

Faculty Position – Cancer Biology (Children’s Research Institute at UT Southwestern)

Postdoctoral Fellow – Pancreatic Cancer (The University of Alabama at Birmingham)

Postdoctoral Position – Pancreatic Ductal Adenocarcinoma (IT University of Copenhagen)

Research Technition – Diabetes, Allergies, and Lung Diseases (Helmholtz Zentrum München)

Postdoctoral Researcher – Endocrinology, Diabetes, and Metabolism (The University of Alabama at Birmingham)

Postdoctoral Fellowship – Regenerative Medicine and Metabolic Biology (Indiana Biosciences Research Institute)

Research Positions – Pancreatic Beta-Cells (Université de Montréal)

Postdoctoral Fellow – Neuroscience and Diabetes (The Child Health Institute of New Jersey)

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