We have investigated the changing rule of serum form of GP73 (sGP73) in different hepato-pathologic processes and identified the sGP73 role in inflammation, fibrosis and carcinogenesis since sGP73 has been regarded as a candidate tumor marker. Quantitative enzyme-linked immunosorbent assay detected sGP73 in 535 subjects with hepatocellular carcinoma (HCC), liver cirrhosis (LC), hepatitis, focal nodular hyperplasia (FNH), angioma, intra-hepatic cholangio-carcinoma (ICC) and metastatic cancer from adenocarcinomas (MC). Median sGP73 in LC was higher than in HCC and hepatitis (p 5 0.001), and sGP73 in all three groups were higher than those in healthy individuals (p < 0.001); sGP73 in LC patients with Child-Pugh class A was lower than in class B and C (p = 0.001), no significant difference was found between early and advanced HCC groups (110.4 lg/L vs. 102.8 lg/L). AFP/GP73 had a sensitivity of 75.8% and specificity of 79.7% with an area under the receiver operating curve (AUROC) of 0.844 vs. 0.812 for AFP (p 5 0.055) with a sensitivity of 95.2% and specificity of 47.1%; in detecting early HCC, AUROC of AFP/GP73 was 0. 804 vs. 0.766 for AFP (p 5 0.086). sGP73 correlated with AST, AST/ALT, ALB, A/G and ALP in LC. The positive rate of sGP73 in angioma, FNH, ICC, and MC was 0, 50, 63.3, 53.3%, respectively; AFP/GP73 was 0.796 with the sensitivity of 81.4% and specificity of 70.0% when differentiating MC from AFP-negative HCC. Increased sGP73 is related to hepatic impairment and chronic fibrosis, and when combined with AFP could improve the differential diagnosis of hepatic diseases.Primary hepatic cancers (PHC) have a high incidence worldwide and are lethal, with $10% surviving >5 years.

Previous population investigations have suggested that the application of curcumin may be associated with decreased incidence and improved prognosis in certain types of cancer. Forkhead box O1 (FOXO1) has been implicated in the regulation of several biological processes, including stress resistance, metabolism, DNA repair, cell cycle and apoptosis. The aims of the present study were to investigate the effects and molecular mechanisms of curcumin on the induction of anti‑proliferation, cell cycle arrest and apoptosis, by FOXO1, in pancreatic cancer cells. The MTT assay and ELISA‑Brdu assay were used to assess cell proliferation. Reverse transcription‑quantitative polymerase chain reaction and western blot analyses were used to detect the expression of PCNA, Ki‑67, B‑cell lymphoma‑2 (Bcl‑2), B‑cell‑associated X protein (Bax), cyclin D1, p21, p27 and FOXO1. Cell apoptosis was detected using a Cell Death ELISA detection kit. A Caspase‑3/9 Fluorescent Assay kit was used to detect caspase activity. The findings revealed that curcumin significantly decreased cell proliferation, which was associated with increased expression of the p21/CIP1 and p27/KIP1 cyclin‑dependent kinase inhibitors, and inhibited expression of cyclin D1. In addition, curcumin induced apoptosis by decreasing the Bcl‑2/Bax protein ratio and increasing caspase‑9/3 activation in the pancreatic cancer cells. Using siRNA against FOXO1, and Akt inhibitor and activator, the present study confirmed that curcumin induced the expression of FOXO1 by inhibition of phosphoinositide 3‑kinase/Akt signaling, leading to cell cycle arrest and apoptosis. In conclusion, these findings offer support for a mechanism that may underlie the anti‑neoplastic effects of curcumin and justify further investigation to examine the potential roles for activators of FOXO1 in the prevention and treatment of pancreatic cancer.

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Pancreatic ductal adenocarcinoma (PDAC) is extremely malignant. Efficient control of cancer growth may substantially improve the survival of PDAC patients. However, no efficient treatments are so far available. Here, we inhibited transforming growth factor β (TGFβ) receptor signaling by overexpression of a key inhibitor of this pathway, SMAD7, in the mouse pancreas, using a recently developed intraductal infusion method. Overexpression of SMAD7 significantly increased growth of both implanted PDAC and PDAC by K-ras modification. Our data thus suggest that TGFβ receptor signaling restrains growth of PDAC, and modulation of TGFβ receptor signaling may be an effective treatment for PDAC.

Due to the lack of a suitable model, research on biliary biology is far behind that on other organs. A mouse model of common bile duct (CBD) dilation (BDD) was first established and compared with CBD ligation mice (BDL). Then, in a transplantation experiment, the dilated CBD of recipient BDD mice was injured by making an elliptical incision and repaired by transplanting a bile duct patch from donor BDD mice. Biochemical and histological changes were analyzed and cell proliferation of the bile duct grafts was determined. Slightly dilated and unblocked CBD with a diameter of 2.89±0.76 mm was obtained in BDD mice, while the CBD diameter was 0.51±0.08 mm in the Sham group and 4.71±0.64 mm in the BDL group on day 14 after surgery. The liver damage was very mild in BDD mice compared with BDL mice, proving that the BDD model could be further used for bile duct transplantation. By cross transplanting the bile duct patch from enhanced green fluorescence protein and wild-type BDD mice, it was found that the CBD injury was well repaired and the cells of the bile duct patch were completely replaced by recipient-derived cells at 12 week after the repair operation. α Smooth muscle actin, Ki67 and cytokeratin 19 immunofluorescence staining showed that the proliferation of bile duct epithelial cells and abundant active fibroblasts were found within the bile duct patch during the regeneration process. Therefore, a reliable new mouse model of bile duct injury and repair was successfully established and can be used in the study of biliary repair mechanisms and tissue engineering of biliary ducts.

In the initiation and progression of pancreatic cancer, DNA methylation plays a critical role. The present study attempts to explore specific prognosis subtypes based on DNA methylation data and develop an epigenetic signature to predict the overall survival (OS) of patients with pancreatic cancer.147 samples were included in the training cohort, whereas the validation cohort included 226 samples. The 298 OS-related methylation sites in the training cohort were selected for consensus clustering, and the authors identified three subtypes with a significant difference in prognosis. Cluster1 was associated with poor OS, low-grade disease and high lymph node involvement. In addition, we identified 33 specific methylation sites in Cluster1. Subsequently, we developed a robust qualitative signature consisting of 14 methylation sites to individually predict OS in the training cohort, and the predictive accuracy of this model was confirmed in the validation cohort. Functional enrichment analysis showed that the selected genes in the model were mainly enriched in known cancer-related pathways. Patients were divided into high- and low-risk groups by the model, and a significant difference in OS was observed between these groups. Classification based on the modeling of a specific DNA methylation site can reveal the heterogeneity of pancreatic cancer and provide guidance for clinicians in predicting the prognosis of pancreatic cancer and providing personalized treatment.

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