ABSTRACT
BACKGROUND/AIMS: PIK3R3 is a regulatory subunit of phosphatidylinositol 3-kinase (PI3K) which plays an essential role in the metastasis of several types of cancer. However, whether PIK3R3 can promote the metastasis of pancreatic cancer (PC) is still unclear. In this study, we characterized the role of PIK3R3 in metastasis of PC and underlying potential mechanisms. METHODS: RT-PCR, western blot, immunofluorescence (IF) and immunohistochemistry (IHC) were applied to investigate the expression of genes and proteins in different cell lines and tissues. To assess the function of PIK3R3 and related mechanisms, the cells with RNAi-mediated knockdown or overexpression were used to perform a series of in vitro and in vivo assays. RESULTS: PIK3R3 was significantly overexpressed in pancreatic cancer tissues, especially in metastatic cancer tissues, as well as in pancreatic cancer cells. Functional assays suggested that overexpression or knockdown of PIK3R3 could respectively promote or suppress the migration and invasion of PC cells in vitro and in vivo. Further mechanism related studies demonstrated that ERK1/2-ZEB1 pathway-triggered epithelial-mesenchymal transition (EMT) might be responsible for the PIK3R3-induced PC cell migration and invasion. CONCLUSION: PIK3R3 could promote the metastasis of PC by facilitating ZEB1 induced EMT, and could act as a potential therapeutic target to limit PC metastasis.
Subject(s)
Epithelial-Mesenchymal Transition , Pancreas/pathology , Pancreatic Neoplasms/pathology , Phosphatidylinositol 3-Kinases/metabolism , Zinc Finger E-box-Binding Homeobox 1/metabolism , Animals , Cell Line , Cell Line, Tumor , Cell Movement , Female , Humans , Mice, Inbred BALB C , Neoplasm Invasiveness/pathology , Neoplasm Metastasis/pathology , Pancreas/metabolism , Pancreatic Neoplasms/metabolism , Phosphatidylinositol 3-Kinases/analysis , Zinc Finger E-box-Binding Homeobox 1/analysisABSTRACT
Postoperative pancreatic fistula (POPF) is a common complication following distal pancreatectomy (DP). However, the risk factors of this complication in patients after DP still remain controversial. The aim of our study is to estimate the association between potential risk factors and POPF. Relevant articles published up to June 21, 2016 were identified via PubMed, EMBASE, Web of Science, and The Cochrane Library. Studies that examined the risk factors of POPF following DP were enrolled. 20 articles (2070 patients) were finally included in this study. The pooled data suggested that patients with soft pancreas, higher Body Mass Index (BMI), blood transfusion, elevated intraoperative blood loss, and longer operative time had a decreased risk for POPF. However, age, gender, malignant pathology, types of stump closure, octreotide therapy, history of diabetes and chronic pancreatitis, splenectomy, multiorgan resection, main duct ligation, preoperative serum albumin levels, PGA felt wrapping, and extended lymphadenectomy could not be regarded as risk factors for POPF. Our analytic data demonstrated that pancreas texture, BMI, blood transfusion, intraoperative blood loss, and operative time were clinical predictor for POPF. This study may assist surgeons to screen patients with high risk of POPF and select appropriate treatment measures.
Subject(s)
Pancreatectomy/adverse effects , Pancreatic Fistula/epidemiology , Postoperative Complications/epidemiology , Female , Humans , Male , Pancreatic Fistula/etiology , Risk FactorsABSTRACT
The mechanism and kinetics of the reactions of CF(3)COOCH(2)CH(3), CF(2)HCOOCH(3), and CF(3)COOCH(3) with Cl and OH radicals are studied using the B3LYP, MP2, BHandHLYP, and M06-2X methods with the 6-311G(d,p) basis set. The study is further refined by using the CCSD(T) and QCISD(T)/6-311++G(d,p) methods. Seven hydrogen-abstraction channels are found. All the rate constants, computed by a dual-level direct method with a small-curvature tunneling correction, are in good agreement with the experimental data. The tunneling effect is found to be important for the calculated rate constants in the low-temperature range. For the reaction of CF(3)COOCH(2)CH(3) +Cl, H-abstraction from the CH(2) group is found to be the dominant reaction channel. The standard enthalpies of formation for the species are also calculated. The Arrhenius expressions are fitted within 200-1000 K as kT(1) =8.4×10(-20) T (2.63) exp(381.28/T), kT(2) =2.95×10(-21) T (3.13) exp(-103.21/T), kT(3) =1.25×10(-23) T (3.37) exp(791.98/T), and kT(4) =4.53×10(-22) T (3.07) exp(465.00/T).
