DTX3L Accelerates Pancreatic cancer Progression via FAK/PI3K/AKT Axis.

DTX3L (Deltex E3 ubiquitin ligase 3 L) is an E3 ubiquitin ligase, a member of the deltex family. It is also known as B-lymphoma and BAL-associated protein (BBAP). DTX3L has been proven to play an important role in various tumor development; however, its role in pancreatic cancer remains unknown. So, we analyzed the DTX3L expression in pancreatic cancer based on the TCGA database and verified it in our samples by qRT­PCR and western blot. We identified that DTX3L was highly expressed in pancreatic cancer, and its expression level was significantly negatively correlated with patients' survival. Using CCK8, colony formation, transwell, and wound healing assays, we found that upregulated DTX3L promotes pancreatic cancer cell proliferation, invasion, and migration. Mechanically, DTX3L combined with EGFR (epidermal growth factor receptor) and prevented the ubiquitination degradation of it. Upregulated EGFR activated the FAK/PI3K/Akt pathway and promoted the progression of pancreatic cancer. Moreover, we found that DTX3L can weaken pancreatic cancer cells' sensitivity to chemotherapy using the orthotopic implant tumor model. In conclusion, DTX3L accelerates pancreatic cancer progression by EGFR dependent FAK/PI3K/Akt pathway activation and may become a potential target for pancreatic cancer treatment.

Long noncoding RNA HOXD-AS1 promotes the progression of pancreatic cancer through miR-664b-3p/PLAC8 axis.

Pancreatic cancer (PC) is one of the most common malignancies worldwide. There are no effective early diagnosis and therapeutic methods for PC. Mounting evidence has shown that lncRNAs promote PC progression. For instance, HOXD-AS1 acts as an oncogenic lncRNA in some digestive tumors. However, its role in PC is unknown. This study aimed to investigate the role of HOXD-AS1 in PC and its underlying mechanisms. Quantitative reverse transcription (qRT­PCR) was used to measure the expression levels of HOXD-AS1, miR-664b-3p, and PLAC8. CCK-8, colony formation, wound healing, and transwell assays were used to assess the effect of HOXD-AS1 on the proliferation, invasion and migration of PC cells. Dual-luciferase reporter and cell function rescue assays were used to verify the regulation relationship of miR-664b-3p and HOXD-AS1 or PLAC8. HOXD-AS1 was significantly upregulated in PC tissues than in paired adjacent tissues. Moreover, HOXD-AS1 was related to the advanced TNM stage. Meanwhile, HOXD-AS1 promoted the proliferation, invasion, and migration of PC cells. Mechanically, HOXD-AS1 upregulated PLAC8 by targeting miR-664b-3p. In conclusion, HOXD-AS1 was upregulated in PC tissues, promoting the proliferation, invasion, and migration of PC cells via the miR-664b-3p/PLAC8 axis.

Clinical significance of changes in AFP, HTATIP2/TIP30, B7-H4 and inflammatory cytokines after transcatheter arterial chemoembolization.

PURPOSE: To explore the clinical significance of changes in alpha-fetoprotein (AFP), HIV-1 TAT interactive protein 2/TAT interactive protein 30 (HTATIP2/TIP30), B7-H4 and inflammatory cytokines after transcatheter arterial chemoembolization (TACE). METHODS: A total of 84 hepatocellular carcinoma (HCC) patients admitted to the Department of Hepatobiliary Surgery and the Department of Interventional Radiology of our hospital from January 1, 2017 to December 31, 2018 were randomly enrolled and divided into an experimental group and a control group according to treatment methods. The expression levels of AFP mRNA, HTATIP2/TIP30, B7-H4 and inflammatory cytokines were detected before and after treatment, the short-term efficacy was followed up and analyzed, and the correlation between the two was statistically analyzed. RESULTS: The AFP expression level in the two groups of patients was lower after treatment than before treatment, this reduction being more obvious in the experimental group (receiving TACE) than in the control group. Although the levels of serum HTATIP2/TIP30 and B7-H4 were decreased after treatment in both groups, and they were lower after treatment than those before treatment in the control group, lower levels were registered in the control group. Both groups of patients had lower expression levels of tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6) after treatment compared with those before treatment, this decrease being more significant in the experimental group than in the control group. Moreover, the total short-term efficacy rate and the improvement rate of the quality of life were higher in the experimental group than in the control group, although no statistical difference in the survival rate was found between the two groups after 1-year follow-up. The serum level of B7-H4 in the group with good efficacy was lower than in the group with poor efficacy before treatment, and it declined in both groups after treatment, with a lower level in the former than in the latter. Furthermore, the group with good efficacy had a lower level of serum HTATIP2/TIP30 than the group with poor efficacy, while both groups had a decreased level after treatment, with a lower level in the former than in the latter. CONCLUSION: Interventional therapy for primary HCC has good short-term efficacy. It can reduce the levels of serum HTATIP2/TIP30, B7-H4, AFP and inflammation-related indexes, improve the liver function and the patients' quality of life.

POTEE stimulates the proliferation of pancreatic cancer by activating the PI3K/Akt/GSK-3ß/ß-catenin signaling.

To explore the role of POTEE in the malignant development of pancreatic cancer and the possible mechanism. POTEE levels in pancreatic cancer samples were detected. The relationship between POTEE level and clinical data of pancreatic cancer patients was analyzed. After knockdown of POTEE or treatment of the GSK-3ß inhibitor, proliferative change in pancreatic cancer cells was assessed. Protein levels of vital genes in the PI3K/Akt/GSK-3ß/ß-catenin signaling influenced by POTEE were examined. POTEE was upregulated in pancreatic cancer samples. High level of POTEE indicated advanced tumor staging, large tumor size, and poor prognosis in pancreatic cancer patients. Knockdown of POTEE or treatment of Tideglusib remarkably attenuated proliferative ability in pancreatic cancer cells. Vital genes in the PI3K/Akt/GSK-3ß/ß-catenin signaling were downregulated by knockdown of POTEE. POTEE stimulates the proliferative ability in pancreatic cancer by activating the PI3K/Akt/GSK-3ß/ß-catenin signaling. High level of POTEE indicates advanced tumor staging, large tumor size and poor prognosis in pancreatic cancer patients.

Prognostic factors in the surgical treatment of caudate lobe hepatocellular carcinoma.

AIM: To evaluate the short- and long-term outcomes of liver resection for caudate lobe hepatocellular carcinoma (HCC). METHODS: We retrospectively analyzed 114 consecutive patients with HCC, originating from the caudate lobe, who underwent resection between January 2001 and January 2007. Univariate and multivariate analyses were performed on several clinicopathologic variables to determine the factors affecting long-term outcome and intrahepatic recurrence. RESULTS: Overall mortality and morbidity were 0% and 18%, respectively. After a median follow-up of 31 mo (interquartile range, 11-66 mo), tumor recurrence had occurred in 76 patients (66.7%). The 1-, 3-, and 5-year disease-free survival rates were 65.7%, 38.1%, and 18.4%, respectively. The 1-, 3-, and 5-year overall survival rates were 76.1%, 54.7%, and 31.8%, respectively. Univariate analysis showed that subsegmental location of the tumor (45.7% vs 16.2%, P = 0.01), liver cirrhosis (12.3% vs 47.9%, P = 0.03), surgical margin (18.5% vs 54.6%, P = 0.04), vascular invasion (37.9% vs 23.2%, P = 0.04) and extended caudate resection (42.1% vs 15.4%, P = 0.04) were related to poorer long-term survival. Multivariate analysis showed that only subsegmental location of the tumor, liver cirrhosis and surgical margin were significant independent prognostic factors. CONCLUSION: Hepatectomy was an effective treatment for HCC in the caudate lobe. The subsegmental location of the tumor, liver cirrhosis and surgical margin affected long-term survival.

[Effect of the amount of portal blood stasis removal on endotoxemia and liver function after liver transplantation].

OBJECTIVE: To investigate the influence of the amount of portal blood stasis removal on endotoxemia and liver function after liver transplantation. METHODS: Forty-seven patients who received liver transplantation from February 2006 to November 2007 were divided into 2 groups according to the amount of portal blood stasis removal during operation: group A (n = 26) 50 ml and group B (n = 21) 200 ml of portal blood stasis removal respectively. The levels of plasma endotoxin, D-lactate, tumor necrosis factor-alpha, interleukin-6, liver function and blood coagulation were examined and analyzed. RESULTS: Under the condition of no significant difference in sex, age, primary liver diseases and Child-pugh's classification, cold ischemic time, total operation and anhepatic time, operation methods, volume of blood loss and transfusion, and all preoperative observations. Most of observations showed the restoration of the patients in group B was better than that in group A. The plasma levels of endotoxin, D-lactate, tumor necrosis factor-alpha, interleukin-6, alanine aminotransferase, aspartate aminotransferase, prothrombin time and activated partial thromboplastin time in group B were significantly lower than those in group A (P < 0.05). The level of plasma prealbumin in group B was significantly higher than that in group A (P < 0.05). CONCLUSIONS: The removal of 200 ml portal blood stasis leads to a better results than that of 50 ml, and it can help alleviate endotoxemia and facilitate the restoration of the liver function after liver transplantation.