Depletion of the gut microbiota decreases pancreatic cancer burden by modulating the immune system
Objectives The gut microbiome significantly outnumbers the human genome. While the latter is non-modifiable, the microbiome changes with nutrition, age, geography and disease-state. Multiple cancers, including pancreatic ductal adenocarcinoma (PDAC), present with changed ‘dysbiotic’ gut microbiota. Whether this dysbiotic state promotes cancer or is a neutral-bystander is unclear. We investigated this relationship in multiple preclinical models of pancreatic and other cancers. (Source: Pancreatology)
Source: Pancreatology - June 1, 2018 Category: Gastroenterology Authors: Vrishketan Sethi, Saba Kurtom, Mohammad Tarique, Shweta Lavania, Zoe Malchiodi, Leonor Hellmund, Bhuwan Giri, Bharti Garg, Sundaram Ramakrishnan, Sulagna Banerjee, Sabita Roy, Ashok Saluja, Vikas Dudeja Tags: Session 11. Molecular mechanisms of pancreatic cancer - free papers Source Type: research
Mutant KRAS-driven cancers depend on PTPN11/SHP2 phosphatase
Objectives The ubiquitously expressed non-receptor protein tyrosine phosphatase SHP2, encoded by PTPN11, is involved in signal transduction downstream of multiple growth factor, cytokine and integrin receptors. Its requirement for complete RAS-MAPK activation and its role as a negative regulator of JAK-STAT signaling have established SHP2 as an essential player in oncogenic signaling pathways. Recently, novel potent allosteric SHP2-inhibitors have been presented as a viable therapeutic option for RTK-driven cancers, but were shown to be ineffective in KRAS mutant tumor cell lines in vitro. (Source: Pancreatology)
Source: Pancreatology - June 1, 2018 Category: Gastroenterology Authors: Dietrich Ruess, Guus Heynen, Katrin Ciecielski, Walter Birchmeier, Roland Schmid, Hana Alg ül Tags: Session 11. Molecular mechanisms of pancreatic cancer - free papers Source Type: research
Impact of cytosolic 5'-nucleotidase 1A on chemotherapeutic resistance in pancreatic cancer
Objectives The nucleoside analogue gemcitabine, still a standard chemotherapeutic agent in metastatic pancreatic cancer, is administered as prodrug and requires sequential phosphorylation to be activated. Cytosolic 5 ’-nucleotidase 1A (Nt5c1A) catalyzes the dephosphorylation of nucleoside monophosphates, thus reversing the initial phosphorylation of gemcitabine. (Source: Pancreatology)
Source: Pancreatology - June 1, 2018 Category: Gastroenterology Authors: Melanie S. Patzak, Elisabeth Hessmann, Vijayalakshmi Kari, Julia Kitz, Shilpa Patil, Frances M. Richards, Duncan I. Jodrell, Steven A. Johnsen, Volker Ellenrieder, Albrecht Neesse Tags: Session 11. Molecular mechanisms of pancreatic cancer - free papers Source Type: research
Reversing pancreatic cancer metastasis through pharmacological targeting of pancreatic stellate cell's dialog with M2 macrophages
Objectives Pancreatic ductal adenocarcinoma (PDAC) presents an exuberant stroma. Stromal activated pancreatic stellate cells (PSC) secrete soluble and extracellular matrix (ECM) proteins that promote cancer cell aggressiveness. (Source: Pancreatology)
Source: Pancreatology - June 1, 2018 Category: Gastroenterology Authors: R émi Samain, Julia Rochotte, Stéphanie Cassant-Sourdy, Aurélie Perraud Perraud, Muriel Mathonnet, Herbert Schmid, Yvan Martineau, Stéphane Pyronnet, Christine Jean, Corinne Bousquet Tags: Session 11. Molecular mechanisms of pancreatic cancer - free papers Source Type: research
Epigenetic mechanisms drive cellular reprogramming in pancreatic carcinogenesis
Objectives Pancreatic acinar cells show an immense cellular plasticity in pancreatitis and pancreatic cancer development. Compared to differentiated acinar cells, progenitor-like acinar-to-ductal metaplasia (ADM) and embryonic acinar cells are highly susceptible towards oncogenic Kras-driven cellular transformation. Given that inflammation-triggered ADM occurs in the absence of genetic mutations, associated transcriptional changes are likely induced by epigenetic modifications. To define epigenetic reprogramming in pancreatic tumor development, we investigated global changes in histone modifications in an in vitro carcinog...
Source: Pancreatology - June 1, 2018 Category: Gastroenterology Authors: Simone Benitz, Ujjwal M. Mahajan, Stefan Czemmel, Sven Nahnsen, G üralp Ceyhan, Julia Mayerle, Christoph W. Michalski, Jörg Kleeff, Ivonne Regel Tags: Session 11. Molecular mechanisms of pancreatic cancer - free papers Source Type: research
