ZNRF2 as an oncogene is transcriptionally regulated by CREB1 in breast cancer models.

E3 ubiquitin ligase Zinc and Ring Finger 2 (ZNRF2) has been demonstrated to be engaged in the development of multiple cancers. Nevertheless, the function of ZNRF2 in breast cancer (BC) still unclear. In this work, we firstly analyzed the differentially expressed genes in BC by bioinformatics and found that ZNRF2 was highly expressed in BC. Consistently, we further confirmed that ZNRF2 was upregulated in BC tissues compared with adjacent normal tissues, and this was positively correlated with the poor prognosis and the higher pathological grades of patients with BC. Functional assays performed on HCC1937 and MCF-7 cells indicated that silencing of ZNRF2 suppressed cell proliferation, as evidenced by the decrease in the expression of cyclin A, PCNA and cyclin D1. Flow cytometry and Hoechst staining showed that knockdown of ZNRF2 induced cell apoptosis, which was verified by the upregulation of apoptosis genes such as Bax, cleaved PARP and Bim. ZNRF2 knockdown also inhibited in vivo tumor growth. But, instead, ZNRF2-overexpressed BC cells exhibited obvious malignant phenotypes. Additionally, we observed that cAMP response element binding protein 1 (CREB1) directly bound to the promoter sequence of ZNRF2 and thus activating its transcription, suggesting that ZNRF2 is transcriptionally regulated by CREB1. Additionally, ZNRF2 knockdown could reverse the proliferation-promoting action of CREB1 on BC cells, Hence, this study demonstrated that ZNRF2 might serve as a prospective therapeutic target for BC.

The choice of operation timing of laparoscopic cholecystectomy (LC) after percutaneous transhepatic gallbladder drainage (PTGBD) for acute cholecystitis: a retrospective clinical analysis.

BACKGROUND: This study aimed to evaluate the timing of laparoscopic cholecystectomy (LC) after percutaneous transhepatic gallbladder drainage (PTGBD). METHODS: Patients with acute moderate to severe cholecystitis treated by LC after PTGBD in the Department of Hepatobiliary and Pancreatic Surgery, Nankai Hospital (N-362) between January 2017 and August 2019were retrospectively enrolled into this study. According to the interval times from PTGBD to LC, the patients were divided into six groups, including group A (105 cases, within 1 week), group B (62 cases, 1-2 weeks), group C (34 cases, 3-4 weeks), group D (54 cases, 5-8 weeks), group E (24 cases, 9-12 weeks), and group F (83 cases, over 12 weeks). The gender, age, hospital stay, duration of operation, rate of conversion to laparotomy, incidence of complications, and hospitalization expenses of the six groups were evaluated and compared. RESULTS: Of the 362 cases of LC, 346 patients were operated successfully (95.6%), 10 were converted to laparotomy (2.8%), 16 had various complications (4.4%), and 2 died (0.6%). There were no significant differences between groups in the gender ratio, complication rate, and rate of conversion to laparotomy. The hospital stay and hospitalization expenses in group A were the least and significantly lower than those in other groups (P<0.01), and the duration of operation in group D was the longest and significantly higher than that in groups A, B, E, and F (P<0.05). CONCLUSIONS: For non-elderly patients diagnosed with acute moderate to severe cholecystitis with an anesthesia risk score [American Society of Anesthesiologists (ASA)] ≤2, LC is recommended to be performed within 1 week after PTGBD surgery. If delayed LC is performed within 2 to 8 weeks after PTGBD, the operation time will be longer due to inflammatory edema and fibrous adhesion of the gallbladder triangle. If PTGBD is performed for more than 2 months and the clinical circumstances are good, delayed LC can be considered to reduce the inconvenience of patients with a long-term catheter as much as possible.

miR-499a promotes PANC-1 cell proliferation by down-regulating PDCD4 expression in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive digestive system tumors, but study of the molecular mechanism of occurrence and development of PDAC is considerably limited. In order to better understand the potential pathogenesis, the differentially expressed miRNAs were screened in PDAC and adjacent tissues using miRNAs microarrays. We found that miR-499a was significantly up-regulated in PDAC tissues compared with adjacent tissues, and protein-protein interaction (PPI) and gene ontology (GO) analyses indicated programmed cell death protein 4 (PDCD4) is a key target gene of miR-499a, which is involved in the regulation of transcription, cellular biosynthetic process, RNA metabolic process, and other multiple biologic processes. Moreover, PDCD4 mRNA and protein expression were obviously down-regulated in PDAC tissues compared with adjacent tissues. In vitro, up-regulating of miR-499a could decrease PDCD4 expression and promote cell proliferation in PANC-1 cells transfected with miR-499a mimics. Similarly, promoting proliferation was also observed in PANC-1 cells transfected with PDCD4 siRNA. In conclusion, we first found miR-499a was significantly up-regulated in PDAC tissues, and we promoted PANC-1 cell proliferation by down-regulating PDCD4 expression.

Comparison of Clinical Efficacy and Complications Between Laparoscopic Partial and Open Partial Hepatectomy for Liver Carcinoma: A Meta-Analysis.

OBJECTIVE: To contrast the clinical effects and complications for the treatment of liver carcinoma in laparoscopic partial hepatectomy (LPH) and open partial hepatectomy (OPH). METHODS: The multiple databases were adopted to search relevant studies, and the articles eventually satisfying the inclusion criteria were included. All the meta-analyses were conducted with the Review Manager 5.3, and to estimate the quality of each article risk of bias table was performed. RESULTS: In the end, 17 studies including 3897 patients were involved, which eventually satisfied the eligibility criteria. The number of samples in LPH group and OPH group were 1723 and 2174, respectively. The results of heterogeneity test suggested that recurrence rate (odds ratio [OR] = -20.11, 95% confidence interval, CI [-35.93 to -4.29], P = .01; P for heterogeneity <.00001, I2 = 100%), hospital days (mean difference (MD) = -2.21, 95% CI [-2.53 to -1.88], P < .000001; P for heterogeneity = .41, I2 = 58%), and blood loss (MD = -68.09, 95% CI [-85.07 to -51.11], P < .00001; P for heterogeneity = .13, I2 = 37%) were significantly different, whereas operating time (MD = 4.00, 95% CI [-17.50 to 25.49], P = .72; P for heterogeneity <.00001, I2 = 99%) and complication events (OR = 0.68, 95% CI [0.46 to 1.01], P = .05; P for heterogeneity = .34, I2 = 11%) between LPH and OPH were insignificantly different. CONCLUSION: This study demonstrated that clinical efficacy of OPH was better than that of LPH to some extent, but LPH was a quicker recovery and less harmful therapy.

Sugiol (127horbar;hydroxyabieta-8,11,13-trien-7-one) targets human pancreatic carcinoma cells (Mia-PaCa2) by inducing apoptosis, G2/M cell cycle arrest, ROS production and inhibition of cancer cell migration.

PURPOSE: Plants produce a diversity of molecular scaffolds with tremendous pharmacological potential. In the present study we evaluated the anticancer activity of the plant-derived natural product sugiol. We also evaluated its effects on apoptosis-related key proteins, cell cycle phase distribution, reactive oxygen species (ROS) and mitochondrial membrane potential (MMP). METHODS: Cell viability was evaluated by MTT assay while clonogenic assay was done to determine the effects of sugiol on the cancer cell colony formation. Flow cytometric measurements were carried out in order to assess the effects of sugiol on cell cycle progression, apoptosis, MMP and ROS generation. RESULTS: Sugiol reduced the cell viability of Mia-PaCa2 human pancreatic cancer cells in a concentration-dependent manner. The IC50 of sugiol on the cell line was 15 µM. The anticancer activity of sugiol was found to be ROS-mediated alterations in MMP, ultimately favoring apoptosis as determined by the annexin V/propidium iodide (PI). Additionally, sugiol caused cell cycle arrest in G2/M phase of the cell cycle and upregulated the expression of Bax, with concomitant downregulation of Bcl-2 expression in comparison to the untreated cells. It also inhibited the migratory capacity of Mia-PaCa2 cells at the IC50 concentration. CONCLUSION: In conclusion our results indicate that sugiol is a potent anticancer molecule and may prove essential in pancreatic cancer therapy.

Expression and clinical significance of EGF and TGF-α in chronic pancreatitis and pancreatic cancer.

BACKGROUND: The purpose of this project was to investigate the expression and clinical significance of epidermal growth factor (EGF) and the transforming growth factor-α (TGF-α) in the occurrence and development of chronic pancreatitis and pancreatic cancer. METHODS: We recruited 31 patients with chronic pancreatitis, 42 with pancreatic cancer, and 20 with normal pancreas in our hospital. Chronic pancreatitis, pancreatic cancer, and normal pancreas expressed EGF and TGF-α mRNAs as well as EGF and TGF-α proteins. RESULTS: Immunofluorescence showed that EGF and TGF-α were expressed in chronic pancreatitis and pancreatic cancer, but the expression levels for both proteins were higher in pancreatic cancer. Variance analysis indicated that the differences in the expression levels of EGF and TGF-α in chronic pancreatitis, pancreatic cancer, and normal pancreas were statistically significant. The abnormally elevated expression of EGF and TGF-α are closely associated with the occurrence and development of chronic pancreatitis and pancreatic cancer. CONCLUSIONS: EGF and TGF-α have important research value as indicators to assess the progression of these conditions and provide a new basis for the clinical diagnosis.

PLAC4 mRNA SNP in non-invasive prenatal testing of Down syndrome.

The purpose of this study was to explore the mRNA expression level of PLAC4 in the maternal plasma and the clinical value of its single nucleotide polymorphism (SNP) rs8130833 in non-invasive prenatal testing (NIPT) of Down syndrome. 40 pregnant women were collected in Tianjin Medical University General Hospital from January 2014 to December 2015. Amniotic puncture karyotype analysis was adapted to determine whether the fetuses with Down syndrome (DS) or not. 20 fetuses were diagnosed with Down syndrome and recorded as the DS group, and 20 fetuses were normal and recorded as the control group. Quantitative reverse transcription-PCR (qRT-PCR) was used to detect the mRNA expression level of PLAC4 both in the whole blood and plasma of pregnant women. A/G polymorphism of rs8130833 was analyzed by pyrosequencing method using the cell-free fetal RNA (cff RNA) in maternal circulation. The mRNA expression level of PLAC4 in DS group was higher than the control group, but the difference was not statistically significant (P > 0.05). A/G polymorphism of rs8130833 was about 2:1 in DS group, and it was nearly 1:1 in control group. The PLAC4 mRNA SNP (rs8130833) has a certain value of research and application in NIPT of DS.

Surgical treatment for locally advanced pancreatic cancer localized in the pancreatic body and tail (report of 11 cases).

OBJECTIVE: To investigate the clinical efficacy of radical resection for pancreatic cancer localized in the pancreatic body and tail. METHODS: From 2009 to 2013, 11 patients with pancreatic cancer localized in the body and tail were treated with sequential radical resection of the tumor and postoperative chemotherapy, and closely followed up. RESULTS: Among the 11 patients, 7 received R0 resection, 4 received R1 resection. In the rest 2 patients, the tumor was removed together with the involved celiac artery and common hepatic artery. There were no postoperative complications, except second surgery for postoperative ischemic necrosis of the gastric antrum in 1 case, and wound infection in another patient. Nine of the 11 patients underwent cyclic chemotherapy with gemcitabine. Abdominal pain was relieved in all postoperative patients. The postoperative median survival time was 28 months, and 1-year and 3-year survival rates were 81.8% and 36.3%, respectively. CONCLUSION: Combination of surgical removal of the tumor with adjuvant chemotherapy can achieve better survival and significantly improve the patients' quality of life.

CSN5 silencing reverses sorafenib resistance of human hepatocellular carcinoma HepG2 cells.

Hepatocellular carcinoma (HCC) is one of the most common tumor types, and is the third leading cause of cancer mortalities worldwide. A large number of patients with HCC are diagnosed at a late stage when the curative treatment of surgical resection and liver transplantation are no longer applicable. Sorafenib has been proved to improve overall survival in advanced HCC; however, drug resistance is common. The present study reported that the CSN5 is correlated with sorafenib resistance of the HCC cell line HepG2/S. Following silencing of CSN5, resistance to sorafenib was reversed, and multi-drug­resistance proteins, including as adenosine triphosphate binding cassette (ABC)B1, ABCC2 and ABCG2 as well as CDK6, cyclin D1 and B­cell lymphoma 2 were downregulated. In addition, it was demonstrated that the integrin beta-1, transforming growth factor­ß1 and nuclear factor­κB pathways were modified by CSN5.