BACKGROUND & AIMS: Diseases of the exocrine pancreas are often associated with perturbed differentiation of acinar cells. MicroRNAs (miRNAs) regulate pancreas development, yet little is known about their contribution to acinar cell differentiation. We aimed to identify miRNAs that promote and control the maintenance of acinar differentiation. METHODS: We studied ...

OBJECTIVES: Emerging evidence from mouse models suggests that mutant Kras can drive the development of pancreatic ductal adenocarcinoma (PDA) precursors from acinar cells by enforcing ductal de-differentiation at the expense of acinar identity. Recently, human genome-wide association studies have identified NR5A2, a key regulator of acinar function, as a susceptibility ...

ABSTRACT. Pancreatic stellate cells (PSCs) and other pancreatic components that play a critical role in exocrine pancreatic diseases are generally identified separately by conventional studies, which provide indirect links between these components. Here, nonlinear optical microscopy was evaluated for simultaneous characterization of these components within a three-dimensional (3-D) tissue environment, ...

Given the failure of chemo- and biotherapies to fight advanced pancreatic cancer, one major challenge is to identify critical events that initiate invasion. One priming step in epithelia carcinogenesis is the disruption of epithelial cell anchorage to the basement membrane which can be provided by hemidesmosomes (HDs). However, the existence ...

Expansion of the pancreatic endocrine cell population occurs during both embryonic development and during post-natal pancreatic growth and regeneration. Mechanisms of the expansion of endocrine cells during embryonic development are not completely understood, and no clear mechanistic link has been established between growth of the embryonic endocrine pancreas and the ...

Chronic pancreatitis is an inflammatory disease that causes progressive destruction of pancreatic acinar cells and, ultimately, loss of pancreatic function. We investigated the role of IκB kinase α (IKKα) in pancreatic homeostasis. Pancreas-specific ablation of IKKα (IkkαΔpan) caused spontaneous and progressive acinar cell vacuolization and death, interstitial fibrosis, inflammation, and ...

Recent evidences suggested that growth and differentiation of pancreatic cell lineages, including the insulin-producing β-cells, depend on proper tissue-architecture, epithelial remodeling and cell positioning within the branching pancreatic epithelium. We recently found that Rho GTPase and its regulator, Stard13 RhoGAP, coordinate morphogenesis with growth in the developing pancreas. Conditional mutation ...

Diphylla ecaudata is a vampire bat that mainly feeds on the blood of birds. This highly specialized diet - hematophagy - is accompanied by a series of morphological changes in the gastro-entero-pancreatic system, since the distribution and relative proportions of different pancreatic endocrine cell types can vary between species due ...

The developmental origin of a pancreatic precursor cell could provide clues to properties that may be crucial to its molecular regulation and therapeutic potential. Previously, lineage tracing experiments showed that multipotent precursors in mouse islets had a pancreatic and not a neural crest developmental origin. However, a different Cre reporter ...

Islet fibrosis, pancreatic β-cell dysfunction, and β-cell apoptosis are features of pancreatic diabetes and type 2 diabetes; however, the underlying mechanisms remain largely unknown. We hypothesized that pancreatic stellate cells (PSCs), a major profibrogenic cell type in the pancreas, might affect the phenotype of pancreatic β-cells. α-smooth muscle actin (a ...

Results from developmental and phylogenetic studies have converged to facilitate insight into two important steps in vertebrate evolution: (1) the ontogenetic origin of articulating elements of the buccal skeleton, i.e. jaws, and (2) the later origins of middle ear impedance-matching systems that convey air-borne sound to the inner ear fluids. ...

Pancreatic adenocarcinoma is often diagnosed when metastatic events have occurred. The early spread of circulating cancer cells expressing the CD44 receptor may play a crucial role in this process. In this study, we have investigated the cellular delivery ability and both in vitro and in vivo anti-tumoural activity of liposomes ...

Pancreatic exocrine cell plasticity can be observed during development, pancreatitis with subsequent regeneration, and also transformation. For example, acinar-ductal metaplasia (ADM) occurs during acute pancreatitis and might be viewed as a prelude to pancreatic intraepithelial neoplasia (PanIN) and pancreatic ductal adenocarcinoma (PDAC) development. To elucidate regulatory processes that overlap ductal ...

The antioxidant and antiglucotoxic effects of Alternanthera paronychioides on pancreatic β-cell were investigated. Antioxidant assays demonstrated that ethanol extracts of A. paronychioides (EEAP) exhibited the highest antioxidant activity, which also had the highest phenolic and flavonoid contents. Two major polyphenolics, ferulic acid and quercetin, were identified from EEAP by HPLC-DAD. ...

Expression of differentiation markers was found to be reduced during ageing of pancreatic cells. Tetrapeptide pancragen stimulates the expression of differentiation factors of acinar (Pdx1, Ptfla) and islet of Langerhans (Pdx1, Pax6, Pax4, Foxa2, NKx2.2) cells in "young" and " aged" cultures. Differentiation of acinar and islet pancreatic cells induced ...

Actin-related protein 2/3 (ARP2/3) complex is an actin nucleator responsible for actin cytoskeleton branching which is essential for efficient cell migration. The expression of the seven ARP2/3 complex subunits was assessed in pancreatic cancer cell lines and in normal pancreatic samples by quantitative RT-PCR. siRNA-mediated silencing was used to study ...

In this issue of Cancer Cell, Kopp and colleagues report that pancreatic ductal cells are largely refractory to the induction of pancreatic neoplasia. Whereas a rare ductal subpopulation may still prove capable of neoplastic transformation, these findings refocus attention on acinar and other non-ductal cell types as initiators of this ...

Tumors are largely classified by histologic appearance, yet morphologic features do not necessarily predict cellular origin. To determine the origin of pancreatic ductal adenocarcinoma (PDA), we labeled and traced pancreatic cell populations after induction of a PDA-initiating Kras mutation. Our studies reveal that ductal and stem-like centroacinar cells are surprisingly ...

AIMS/HYPOTHESIS: The main objective of this work was to discover new drugs that can activate the differentiation of multipotent pancreatic progenitors into endocrine cells. METHODS: In vitro experiments were performed using fetal pancreatic explants from rats and mice. In this assay, we examined the actions on pancreatic cell development of ...

Acute pancreatitis is an inflammatory disease with no specific treatment. One of the main reasons behind the lack of specific therapy is that the pathogenesis of acute pancreatitis is poorly understood. During the development of acute pancreatitis, the disease-inducing factors can damage both cell types of the exocrine pancreas, namely ...

Grape seed phenolic extract (GSE) is predicted to have health benefits, even though its bioavailability, including digestibility, permeability and ultimate metabolism, are still poorly understood. In vitro gastric and pancreatic digestion and in vitro ileal and faecal fermentation were combined with Caco-2 cell permeability studies for GSE samples. Qualitatively, there ...

BACKGROUND: High serum immunoglobulin G4 (IgG4) levels and infiltration of IgG4-positive cells are characteristic of Type 1 autoimmune pancreatitis (AIP). We previously reported that increased regulatory T cells (Tregs) may regulate IgG4 production in AIP. Although an increased serum IgG4 concentration is observed in some patients with pancreatic ductal adenocarcinoma ...

Background: Pancreatic cancer is one of the most deadly malignancies with insufficient therapeutic options and poor outcome. Cancer stem cells (CSCs) are thought to be responsible for progression and therapy resistance. We investigated the potential of pancreatic cell lines for CSC research by analyzing to what extent they contain CSC ...

OBJECTIVES: Copper-based compounds have been used as agricultural fungicides for many years. Their use in Australia is escalating with increase in the scale of planting and associated pest problems. The objective of this study was to identify viticulture activities associated with high exposure to foliage sprays. It would be determined ...

Pancreatic ductal adenocarcinoma is believed to arise from precursor lesions termed pancreatic intraepithelial neoplasia (PanIN). Mouse models have demonstrated that targeted expression of activated K-ras to mature acinar cells in the pancreas induces the spontaneous development of PanIN lesions; implying acinar-to-ductal metaplasia (ADM) is a key event in this process. ...

NGO0579 is annotated copA in the Neisseria gonorrhoeae chromosome, suggesting that it encodes a cation-transporting ATPase specific for copper ions. Compared to wild-type cells, a copA mutant was more sensitive to killing by copper ions but not to other transition metals. The mutant also accumulated a greater amount of copper, ...

Comment on: Rizkallah R, et al. Cell Cycle 2011; 10:3327-36.

At present, no effective chemotherapy for pancreatic neuroendocrine carcinoma (PNEC) exists. However, anti-angiogenic therapy is expected to be effective for PNEC, a hypervascular tumor. We treated PNEC and hypovascular pancreatic ductal cell carcinoma (DCC) cell lines with the anti-vascular endothelial growth factor (VEGF) antibody bevacizumab, and compared the antitumor effect ...

We report here the identification and characterization of two zinc uptake systems, ZurAM and ZinABC, in the intracellular pathogen Listeria monocytogenes. Transcription of both operons was zinc responsive and regulated by the zinc-sensing repressor Zur. Deletion of either zurAM or zinA had no detectable effect on growth in defined media, ...

Friedreich ataxia is a hereditary neurodegenerative disease caused by reduced expression of mitochondrial frataxin. Frataxin deficiency causes impairment in respiratory capacity, disruption of iron homeostasis and hypersensitivity to oxidants. Although the redox properties of NAD (nicotinamide adenine dinucleotide; NAD+ and NADH) are essential for energy metabolism, only few results are ...

Fumarate hydratase (FH) is a tumor suppressor, but how it acts is unclear. Two reports in this issue of Cancer Cell reveal that FH deficiency leads to succination of Keap1, stabilization of Nrf2, and induction of stress-response genes including HMOX1, which is important for the survival of FH-deficient cells.

Although zinc is an essential micronutrient for all living organisms, zinc is harmful to cells at high levels. In the presence of excess zinc, plants exhibit several major symptoms, including root growth inhibition, abnormal root hair morphology, and chlorosis. To dissect the molecular mechanisms underlying the effects of excess zinc ...

Comment on: Puca R, et al. Cell Cycle 2011; 10:1679-89.

Inherited glucose-6-phosphate isomerase (GPI) deficiency is the second most frequent glycolytic erythroenzymopathy in humans. Patients present with non-spherocytic anemia of variable severity and with neuromuscular dysfunction. We previously described Chinese hamster (CHO) cell lines with mutations in GPI and loss of GPI activity. This resulted in a temperature sensitivity and ...

Human diploid fibroblasts (HDFs) exposed to subcytotoxic concentrations of oxidative or stressful agents, such as hydrogen peroxide, tert-butylhydroperoxide, or ethanol, undergo stress-induced premature senescence (SIPS). This condition is characterized by the appearance of replicative senescence biomarkers such as irreversible growth arrest, increase in senescence-associated β-galactosidase (SA β-gal) activity, altered cell ...

We identified two proteins, Pex25 and Rho1, which are involved in reintroduction of peroxisomes in peroxisome-deficient yeast cells. These are, together with Pex3, the first proteins identified as essential for this process. Of the three members of the Hansenula polymorpha Pex11 protein family-Pex11, Pex25, and Pex11C-only Pex25 was required for ...

We present the design, synthesis, spectroscopy, and biological applications of Mitochondrial Coppersensor-1 (Mito-CS1), a new type of targetable fluorescent sensor for imaging exchangeable mitochondrial copper pools in living cells. Mito-CS1 is a bifunctional reporter that combines a Cu(+)-responsive fluorescent platform with a mitochondrial-targeting triphenylphosphonium moiety for localizing the probe to ...

We have demonstrated that reducing zinc availability with the extracellular chelator diethylenetriaminepentaacetic acid (DTPA) causes rapid inhibition of cellular zinc efflux in H4IIE hepatoma cells but increases zinc efflux in primary hepatocytes. Similar differences were also observed between the rat anterior pituitary cell line GH3 and primary anterior pituitary cells. ...

Transforming growth factor-beta (TGF-β) mediates several and sometime opposite effects in epithelial cells, inducing growth inhibition, and apoptosis but also promoting an epithelial to mesenchymal transition (EMT) process, which enhances cell migration and invasion. TGF-β plays relevant roles in different liver pathologies; however, very few is known about its specific ...

Altered expression of some members of the TRP ion channel superfamily has been associated with the development of pathologies like cancer. In particular, TRPM4 levels are reportedly elevated in diffuse large B-cell non-Hodgkin lymphoma, prostate, and cervical cancer. However, whether such changes in TRPM4 expression may be relevant to genesis ...

It is known that the roughness of titanium surfaces affects cell proliferation and differentiation. However, the mechanisms mediating the cellular responses to surface topography are only partially understood. The present study investigated whether Wnt canonical signaling, an important pathway in determining cell fate, is modulated by surface roughness. This study ...

Exposure to long-chain saturated fatty acids (SFAs; e.g. palmitate) induces apoptosis in pancreatic β cells, a process that may contribute to the development of type 2 diabetes. Under palmitate treatment, β cells undergo a so-called endoplasmic reticulum (ER) stress that can be counteracted by the unfolded protein response (UPR). The ...

Aberrant activation of the Wnt/β-catenin signaling pathway promotes osteosarcoma tumorigenesis and metastasis. In this study, we tested the hypothesis that osteosarcoma progression may be delayed by disrupting the Wnt/β-catenin pathway using small molecule inhibitors such as curcumin and PKF118-310. Effective inhibitions of the Wnt/β-catenin pathway by curcumin and PKF118-310 in ...

Developmental insults during gestation, such as under-nutrition, are known to restrict the number of beta cells that form in the fetal pancreas and are maintained in adulthood, leading to increased risk of type 2 diabetes. There are now substantial data indicating that glucocorticoids mediate this effect of under-nutrition on beta ...

The present study addressed the effect of the dipeptidyl peptidase-4 (DPP-4) inhibitor vildagliptin ((1-[[(3-hydroxy-1-adamantyl) amino] acetyl]-2-cyano-(S)-pyrrolidine), LAF237) on pancreatic beta cell mass in neonatal rats. Newborn rats were treated orally with vildagliptin (60mg/kg) or vehicle once daily for 19days starting from postnatal day 2. Pancreatic immunohistochemistry and morphometric analysis were ...

To compare the effects of glucocorticoids and thyroid hormones on the regulation of the beta cell mass in the pancreas, the rats were treated and analyzed for cell cycle changes in islet and duct cells as a source for beta cell neogenesis. Different rat pancreases were morphometrically analyzed after immunohistochemical ...

Past studies on β-catenin in cancer cells focused on nuclear localized β-catenin and its involvement in the Wnt pathway. Our goal here was to investigate the function of β-catenin in both the cytoplasm and nucleus on the regulation of MT1-MMP expression and activity. We found that β-catenin in MDCK non-cancer ...

β-Cell regeneration declines with aging, but the molecular mechanisms controlling β-cell replication in humans are not well understood. We compared the expression of selected cell cycle proteins in prenatal and adult tissue and examined the association of these proteins with β-cell replication. Pancreatic tissue from a total of 20 human ...

Serum response factor (SRF) regulates transcription of the immediate early genes and triggers proliferation, migration and differentiation in several types of cells. We examined the role of SRF in HCC by transfecting the SRF cDNA in HLE cells and the SRF anti-sense cDNA in sarcomatoid HCC cells. The overexpression of ...

The Wnt/β-catenin pathway has been implicated in leukemogenesis. We found β-catenin abnormally accumulated in both human acute T cell leukemia Jurkat cells and human erythroleukemia HEL cells. β-Catenin can be significantly down-regulated by the Janus kinase 2 specific inhibitor AG490 in these two cells. AG490 also reduces the luciferase activity ...