Serotonin-RhoA/ROCK axis promotes acinar-to-ductal metaplasia in caerulein-induced chronic pancreatitis.
Serotonin-RhoA/ROCK axis promotes acinar-to-ductal metaplasia in caerulein-induced chronic pancreatitis. Biomed Pharmacother. 2020 Feb 15;125:109999 Authors: Tao X, Chen Q, Li N, Xiang H, Pan Y, Qu Y, Shang D, Go VLW, Xue J, Sun Y, Zhang Z, Guo J, Xiao GG Abstract The underlying molecular mechanisms of chronic pancreatitis (CP) developing into pancreatic ductal adenocarcinoma (PDAC) remain largely unknown. Here we show that the level of serotonin in mouse pancreatic tissues is upregulated in caerulein-induced CP mice. In vitro study demonstrates that serotonin promotes the formation of acinar-to-ductal metaplasia (ADM) and the activation of pancreatic stellate cells (PSCs), which results from the activation of RhoA/ROCK signaling cascade. Activation of this signaling cascade increases NF-κB nuclear translocation and α-SMA expression, which further enhance the inflammatory responses and fibrosis in pancreatic tissues. Intriguingly, quercetin inhibits both ADM lesion and PSCs activation in vitro and in vivo via its inhibitory effect on serotonin release. Our findings underscore the instrumental role of serotonin-mediated activation of RhoA/ROCK signaling pathway in development of PDAC from CP and highlight a potential to impede PDAC development by disrupting tumor-promoting functions of serotonin. PMID: 32070876 [PubMed - as supplied by publisher]
ConclusionsThe success rate of EMSP for mALO was high in patients with poor general conditions due to advanced-stage malignant tumors and it was able to be safely performed, suggesting its high clinical efficacy. The incidence of mALO recurrence after EMSP was low.
Publication date: March 2020Source: Chinese Journal of Natural Medicines, Volume 18, Issue 3Author(s): Xiao FU, Neng TANG, Wei-Qi XIE, Liang MAO, Yu-Dong QIU
Publication date: Available online 29 February 2020Source: Practical Radiation OncologyAuthor(s): Amanda J. Koong, Diego A.S. Toesca, J. Richelcyn M. Baclay, Erqi L. Pollom, Rie von Eyben, Albert C. Koong, Daniel T. Chang
Publication date: 31 March 2020Source: Cell Reports, Volume 30, Issue 13Author(s): Sneha Shah, Gemma Molinaro, Botao Liu, Ruijia Wang, Kimberly M. Huber, Joel D. Richter
Publication date: Available online 31 March 2020Source: CellAuthor(s): Marcus Ruscetti, John P. Morris, Riccardo Mezzadra, James Russell, Josef Leibold, Paul B. Romesser, Janelle Simon, Amanda Kulick, Yu-jui Ho, Myles Fennell, Jinyang Li, Robert J. Norgard, John E. Wilkinson, Direna Alonso-Curbelo, Ramya Sridharan, Daniel A. Heller, Elisa de Stanchina, Ben Z. Stanger, Charles J. Sherr, Scott W. Lowe
Publication date: Available online 31 March 2020Source: Clinica Chimica ActaAuthor(s): Yueting Xiong, Chao Shi, Xiaohui Liu, Pengyuan Yang
Conditions: Breast Cancer; Ovarian Cancer; Pancreatic Cancer; Metastatic Prostate Cancer Interventions: Behavioral: In Person Counseling; Behavioral: Educational Video Sponsors: Dana-Farber Cancer Institute; Ambry Genetics Not yet recruiting
Condition: Metastatic Pancreatic Ductal Adenocarcinoma Interventions: Drug: Relacorilant, 100 mg and 25 mg; Drug: Nab paclitaxel Sponsor: Corcept Therapeutics Not yet recruiting
CONCLUSION: Our study showed that Tim-3 might play an important role in the development of AP through regulating the inflammatory response. PMID: 32224541 [PubMed - in process]