Drug-eluting bead transarterial chemoembolization (TACE) exhibits superior efficacy and equal tolerance to conventional TACE in hepatocellular carcinoma patients with conventional TACE history.

OBJECTIVE: Multiple conventional transarterial chemoembolization (cTACE) procedures would cause treatment resistance in hepatocellular carcinoma (HCC) patients, whether drug-eluting bead transarterial chemoembolization (DEB-TACE) would resolve this issue is a necessary topic. Thus, this study aimed to compare the efficacy and safety between DEB-TACE and cTACE in HCC patients with cTACE treatment history. METHODS: Totally, 134 HCC patients with cTACE treatment history were retrospectively reviewed. They were categorized into DEB-TACE group (N = 70) and cTACE group (N = 64) based on the current treatment they received. RESULTS: After 1-month treatment, DEB-TACE group exhibited an elevated objective response rate (ORR) (71.9% vs. 47.3%, P = 0.008) while similar disease control rate (DCR) (93.0% vs. 81.8%, P = 0.074) compared to cTACE group. Besides, after 3-month treatment, DEB-TACE group also displayed higher ORR (68.4% vs. 44.1%, P = 0.038) and DCR (81.6% vs. 58.8%, P = 0.034) compared to cTACE group. Furthermore, the median progression-free survival (PFS) (11.5 months vs. 6.5 months P = 0.014) and overall survival (OS) (18.5 months vs. 13.0 months, P = 0.025) were longer in DEB-TACE group compared to cTACE group. Moreover, DEB-TACE (vs. cTACE) independently correlated with prolonged PFS (P = 0.021) and OS (P = 0.017) after adjustment by multivariate Cox's regression. Besides, most of liver function indexes were similar before and after treatment between these two groups. Also, the commonly observed adverse events were pain, fever, nausea/vomiting and blood pressure elevation with similar incidence between these two groups (all P > 0.050). CONCLUSION: DEB-TACE exhibits superiority over cTACE in HCC patients with cTACE treatment history.

Bakkenolide­IIIa ameliorates lipopolysaccharide­induced inflammatory injury in human umbilical vein endothelial cells by upregulating LINC00294.

Inflammation, which causes injury to vascular endothelial cells, is one of the major factors associated with atherosclerosis (AS); therefore, inhibition of endothelial inflammation is a key step toward preventing AS. The present study aimed to investigate the effects of bakkenolide­IIIa (Bak­IIIa), an important active component of bakkenolides, on endothelial inflammation, as well as the mechanisms underlying such effects. Lipopolysaccharide (LPS)­damaged human umbilical vein endothelial cells (HUVECs) were treated with Bak­IIIa. The results of the MTT assay and enzyme­linked immunosorbent assay indicated that Bak­IIIa significantly alleviated survival inhibition, and decreased the levels of LPS­induced TNF­α, interleukin (IL)­1ß, IL­8, and IL­6. Furthermore, long noncoding RNA (lncRNA) microarray analyses revealed 70 differentially expressed lncRNAs (DELs) in LPS­damaged HUVECs treated with Bak­IIIa. lncRNA target prediction results revealed that 44 DELs had 52 cis­targets, whereas 12 DELs covered 386 trans­targets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes analyses of the trans­targets indicated that three GO terms were associated with inflammation. Therefore, 17 targets involved in these GO terms and six relevant DELs were screened out. Validation via reverse transcription­quantitative PCR indicated that the fold change of NR_015451 (LINC00294) was the highest among the six candidates and that overexpression of LINC00294 significantly alleviated LPS­induced survival inhibition and inflammatory damage in HUVECs. In conclusion, Bak­IIIa ameliorated LPS­induced inflammatory damage in HUVECs by upregulating LINC00294. Thus, Bak­IIIa exhibited potential for preventing vascular inflammation.

Long non-coding RNA BCAR4 aggravated proliferation and migration in esophageal squamous cell carcinoma by negatively regulating p53/p21 signaling pathway.

Long non-coding RNA breast cancer antiestrogen resistance 4 (lncRNA BCAR4) is an independent factor on the survival prognosis of patients with multiple cancers. However, the role of lncRNA BCAR4 in esophageal squamous cell cancer (ESCC) remains unknown. Here, we unraveled that lncRNA BCAR4 was upregulated in ESCC and predicted poor prognosis. Functionally, lncRNA BCAR4 knockdown induced cell apoptosis and G1/S arrest, while inhibited cell proliferation and migration in vitro; conversely, overexpressing lncRNA BCAR4 promoted proliferation and metastasis. Mechanistically, lncRNA BCAR4 sponged miR-139-3p to upregulate ELAVL1, thereby inhibiting p53/p21 pathway in ESCC cells. In conclusion, lncRNA BCAR4 promotes ESCC tumorigenesis via regulating p53/p21 signaling pathway and develops a brand-new biomarker and medicine target for ESCC.

Integrative bioinformatics analysis identifies LINC01614 as a potential prognostic signature in esophageal cancer.

BACKGROUND: Esophageal cancer (EC) is one of the most common gastrointestinal cancers and the incidence is on the increase in recent years. The aim of the present study was to assess novel long non-coding RNA (lncRNA) biomarkers for the prognosis of EC through the analysis of gene expression microarrays. METHODS: Three datasets (GSE53622, GSE53624, and GSE53625) were downloaded from the Gene Expression Omnibus (GEO) database and EC patients' clinical information were from The Cancer Genome Atlas (TCGA) databases. Differentially expressed genes (DEGs) were screened by comparing tumor tissues with normal tissues using limma R package. The Gene Expression Profiling Interactive Analysis 2 (GEPIA2) database was used to obtain the novel lncRNAs and their co-expression genes in EC and these were visualized with the Cytoscape software. The Kyoto Encyclopedia of Genes and Genomes (KEGG) Orthology Based Annotation System (KOBAS) database was used to analyze the functions enrichment of selected DEGs. Cell Counting Kit-8 (CCK8) and Transwell assays were used to further confirm the function of target lncRNAs. RESULTS: We identified 24 differentially expressed (DE) lncRNAs and 659 DE mRNAs from the intersection of GEO and TCGA databases. And we found that only LINC01614 was concerned with a candidate prognostic signature in EC. "Extracellular matrix (ECM)-receptor interaction" and "PI3K-Akt signaling pathway" were observed, and we constructed a lncRNA-mRNA co-expression network for EC that includes LINC01614 and 64 mRNAs. The results of CCK8 and Transwell assays showed that suppression of LINC01614 inhibited EC cell proliferation and migration. CONCLUSIONS: Our study might provide LINC01614 as a novel lncRNA biomarker for diagnosis and prognosis in EC.

LncRNA CACS15 contributes to oxaliplatin resistance in colorectal cancer by positively regulating ABCC1 through sponging miR-145.

Increasing evidence suggests that long non-coding RNAs (lncRNAs) are implicated with chemoresistance of cancers. However, their functional role and molecular mechanisms in colorectal cancer (CRC) chemoresistance are still largely unclear. In this work, we aimed to investigate the functional role of lncRNA cancer susceptibility candidate 15 (CASC15) in oxaliplatin (OXA) resistance of CRC and reveal the underlying molecular mechanism. Our results discovered that CASC15 was up-regulated in OXA-resistant CRC tissues and cells. Patients with high CASC15 expression level had a poor prognosis. CASC15 knockdown re-sensitized HT29/OXA and HCT116/OXA cells to OXA. Moreover, CASC15 could act as a competing endogenous RNA (ceRNA) to de-repress ABCC1 expression through sponging miR-145. miR-145 overexpression or ABCC1 knockdown could mimic the functional role of down-regulated CACS15 in OXA resistance, which was counteracted by CASC15 overexpression. Furthermore, CASC15 knockdown facilitated OXA sensitivity of OXA-resistant CRC cells in vivo. In summary, CASC15 silencing overcame OXA resistance of CRC by regulating miR-145/ABCC1 axis, providing a potential therapeutic target for CRC chemoresistance.

A single-center experience in the endovascular treatment of carotid siphon aneurysms using the Willis covered stent: a retrospective analysis.

OBJECTIVE: To report the clinical results and initial clinical experience of endovascular isolation with the Willis covered stent for carotid siphon aneurysms. METHODS: Between November 2013 and December 2016, a total of 57 patients who presented with carotid siphon aneurysms were treated with the Willis covered stent. Results of the procedures, technical events, and complications were recorded. Clinical and imaging follow-ups were performed at 3 months following the endovascular procedures. RESULTS: Placement of the Willis covered stent was successful in all patients. Immediate angiography revealed complete exclusion of aneurysms in 48 patients (84%), while endoleak occurred in nine patients (16%). Procedure-related complications occurred in three cases, including displacement of the covered stent in one patient, acute in-stent thrombosis in one patient, and microwire-related intracranial hemorrhage in one patient. Angiographic follow-ups were done in 49 patients, with complete exclusion of aneurysms in 47 patients. Endoleak was present in two patients. No aneurysm recurrence occurred. Forty-four patients showed good parent artery patency, while the other five patients showed mild to moderate asymptomatic in-stent stenosis. During the follow-up period, no ischemic or hemorrhagic event occurred. The modified Rankin Scale scores at follow-up were 0-2 in 56 patients and >2 in one patient. CONCLUSIONS: The treatment of siphon aneurysms with Willis covered stent implantation resulted in satisfactory clinical outcomes. The Willis covered stent seems safe and feasible for the treatment of siphon aneurysms, which still needs to be confirmed by longer follow-up periods and controlled studies with larger samples.

Endovascular isolation of intracranial blood blister-like aneurysms with Willis covered stent.

OBJECTIVE: Intracranial blood blister-like aneurysm (BBA) is a rare type of aneurysm that lacks all layers of the arterial wall. These fragile aneurysms have the propensity to rupture with minimal manipulation, which makes them hazardous and difficult to treat. The present study evaluated the safety and feasibility of endovascular treatment of BBAs with the Willis covered stent. MATERIALS: Thirteen patients (7 men and 6 women, age range 28-68 years) who presented with ruptured BBAs and were treated with the Willis covered stent were retrospectively reviewed. Results of the procedures and treatment-related complications were recorded. Angiographic and clinical follow-ups were performed 4-6 months after the procedure. RESULTS: Placement of the covered stent was successful in all patients. Immediate angiography showed complete aneurysm occlusion in 12 patients while one patient showed a mild endoleak. This high rate of aneurysm exclusion ensured the security of postoperative antiplatelet treatment. Occlusion of the ophthalmic artery occurred in two patients and occlusion of the anterior choroidal artery occurred in one patient; however, none of them showed acute or delayed clinical symptoms. Thrombosis, aneurysm rupture, and other complications did not develop in any case. Angiographic follow-up showed complete aneurysm exclusion without aneurysm recurrence in any patients. Only two patients showed asymptomatic mild to moderate in-stent stenosis. All patients had satisfactory clinical outcomes (modified Rankin Scale score ≤1). CONCLUSIONS: Willis covered stent implementation may be safe and feasible for BBAs. This strategy might be a promising option for this high-risk type of aneurysm.

ROBO3 promotes growth and metastasis of pancreatic carcinoma.

Pancreatic carcinoma is a highly lethal malignancy with an extremely poor prognosis. Recent genome-wide studies have implicated axon guidance pathways, including the SLIT/ROBO pathway, in pancreatic tumor development and progression. Here we showed that ROBO3 expression is up-regulated in pancreatic cancer tissue samples and cell lines. Over-expression of ROBO3 promotes pancreatic cancer cell growth, invasion and metastasis in vitro and in mouse xenograft tumor models. We identified miR-383 as a suppressor of ROBO3, and revealed its expression to be inversely correlated with ROBO3. Over-expression of ROBO3 activates Wnt pathway components, ß-catenin and GSK-3, and the expression of markers indicating an EMT. By means of immunoprecipitation, we revealed an interaction between Wnt inhibitor SFRP and ROBO3 in pancreatic cancer cell lines. Our work suggests that ROBO3 may contribute to the progression of pancreatic cancer by sequestering Wnt inhibitor SFRP, which in turn leads to increased Wnt/ß-catenin pathway activity. We also confirmed that ROBO3 increases with clinical grade and miR-383 expression is inversely correlated to that of ROBO3.

Short time tripterine treatment enhances endothelial progenitor cell function via heat shock protein 32.

The dysfunction of endothelial progenitor cells (EPCs) limits their potential for the treatment of ischemia and atherosclerosis. Therefore, we investigated the effect of tripterine on EPC function and examined the underlying mechanisms. The effect of tripterine, an active component of Tripterygium wilfordii Hook, on the enhancement of EPC function and the efficiency of EPC transplantation was investigated in vitro and in vivo. Treatment of EPCs with tripterine at 2.5 µM for 4 h inhibited oxidized low-density lipoprotein (ox-LDL) induced ROS production, cell apoptosis, and cell senescence and improved the migration and tube formation capacities of EPCs treated with ox-LDL (200 µg/ml). In vivo studies showed that tripterine conditioning of EPCs administered to ischemic foci improved blood perfusion and microvascular density in a mouse hindlimb ischemia model. Examination of the underlying mechanisms indicated that the effect of tripterine is mediated by the induction of heat shock protein 32 expression and the inhibition of JNK activation. The present results are of clinical significance because they suggest the potential of tripterine as a therapeutic agent to improve the efficacy of EPC transplantation for the treatment of ischemic diseases.

Expression of Rab25 correlates with the invasion and metastasis of gastric cancer.

The objective of this study was to determine the expression of the important vesicle trafficking-regulating factor Rab25 in human gastric cancer tissues, to analyze the correlation between Rab25 protein expression with gastric cancer occurrence and development, and to discuss the correlation of Rab25 protein expression with gastric cancer cell metastasis. The overall aim was to provide experimental evidence that can be used to design future biological treatments of human gastric cancer. Human gastric cancer tissue and the adjacent normal gastric tissue were surgically removed, and immunohistochemistry and Western blotting were used to detect Rab25 protein expression. The correlation between Rab25 protein expression with the development and pathological characteristics of gastric cancer was analyzed. Using RNAi, Rab25 expression was reduced in the gastric cancer cell line MGC80-3, and the changes in MGC80-3 cell invasiveness were then monitored. Immunohistochemistry showed that the Rab25 protein expression rates were 78.21% and 23.08% in gastric carcinoma and the adjacent normal gastric tissue, respectively. Immunohistochemistry and Western blot results showed that Rab25 protein expression in gastric cancer was significantly higher than in adjacent normal gastric tissues (P<0.01). Less differentiated gastric cancer cells had higher expression of Rab25 protein (P<0.01). Gastric carcinomas from patients with a late pathological stage (III-IV) had significantly higher Rab25 protein expression than early stage (I-II) patients (P<0.01). Gastric carcinomas from patients with lymph node metastasis had significantly higher Rab25 protein expression than lymph node metastasis-free patients (P<0.01). Gastric carcinomas from patients with distant metastases had significantly higher Rab25 protein expression than the distant metastasis-negative patients (P<0.01). Rab25 protein expression in gastric cancer was not affected by the patients(,) sex, age, or tumor size (P>0.05). MGC80-3 cells transfected with Rab25 siRNA had significantly lower Rab25 protein expression (P<0.01) and a significantly lower number of cells that passed through a Transwell chamber compared with non-transfected controls and the transfected control group (P<0.01). Rab25 protein expression is associated with the development of gastric cancer. siRNA knockdown of Rab25 protein expression in MGC80-3 gastric cancer cells reduced MGC80-3 cell invasiveness and provided experimental evidence for potential future biological treatment strategies of human gastric cancer.

A phase II study of intra-arterial chemotherapy of 5-fluorouracil, cisplatin, and mitomycin C for advanced nonresectable gastric cancer.

The best choice of chemotherapy regimen for patients with advanced gastric cancer (AGC) is still a matter of controversy and requires further investigation. This study was performed to evaluate the efficacy and safety of intra-arterial infusion chemotherapy of 5-fluorouracil 1000 mg/m, cisplatin 50 mg/m, and mitomycin C 10 mg/m (FCM) repeated every 6 weeks, as first-line treatment for AGC. Forty-seven (95.9%) of the 49 patients were assessable for response. Four cases of complete response and 28 cases of partial response were confirmed, giving an overall response rate of 65.3% [95% confidence interval (CI): 52.0-78.6%]. The median time to progression and overall survival for all patients was 8.3 months (95% CI: 6.8-9.8 months) and 14.5 months (95% CI: 12.0-17.0 months). The estimate of overall survival at 12 and 24 months was 55.1% (95% CI: 41.2-69.0%) and 18.4% (95% CI: 7.5-29.2%), respectively. Most patients experienced neutropenia during their course of therapy with 21.3% of patients (n = 10) for grade 3/4 neutropenia. Grade 3 stomatitis, lethargy, and palmar-plantar erythema were observed in two (4.3%), eight (17.0%), and one (2.1%) patients, respectively. Yet, no grade 4 nonhematological toxicity was observed. Intra-arterial infusion chemotherapy of 5-fluorouracil 1000 mg/m, cisplatin 50 mg/m, and mitomycin C 10 mg/m is a tolerated treatment modality with promising activity in patients with previously untreated AGC.

Combination therapy with transarterial chemoembolization and interferon-alpha compared with transarterial chemoembolization alone for hepatitis B virus related unresectable hepatocellular carcinoma.

BACKGROUND AND AIMS: The present study was carried out to test the hypothesis that interferon-alpha (IFN-alpha) treatment would reduce or postpone the recurrence rate and improve the overall survival rate in patients after transarterial chemoembolization (TACE) treatment of hepatitis B virus (HBV) related unresectable hepatocellular carcinoma (HCC). METHODS: 216 patients with unresectable HBV-related HCC were randomized into a TACE group and a TACE-IFN group, each group had 108 patients. In the TACE-IFN group, patients received IFN-alpha1b at a dose of 3 million units (mu) three times a week by intramuscular injection one week after/before TACE treatment, for 48 weeks. RESULTS: The median disease-free survival in the TACE-IFN treatment group was 23.6 months (95% CI: 21.4-25.8) and 20.3 months (95% CI: 15.8-24.8) in the TACE group (P = 0.027). The disease free rate at 24 months in the TACE group was lower than in the TACE-IFN group (39.8% vs 59.3%, P = 0.004). The median overall survival was 29 months (95% CI: 27.5-32.1) in the TACE-IFN group and 26 months (95% CI: 20.1-31.9) in the TACE group (P = 0.003). The 2-year overall survival in the TACE-IFN group was higher than in the TACE group (72.2% vs 52.8%, P = 0.003). CONCLUSIONS: IFN-alpha treatment reduced recurrence and improved the survival of patients after TACE treatment of HBV-related HCC, with acceptable toxicities.

[Long-term outcome of interventional therapy for malignant biliary obstruction: a retrospective analysis of 109 cases].

OBJECTIVE: To evaluate the long-term outcome and its relative influenced factors of interventional therapy in dealing malignant biliary obstruction (MBO). METHOD: 109 MBO patients, 54 males and 55 females, aged (71 +/- 12), underwent interventional therapy: 55 patients received percutaneous transhepatic cholangiography and drainage (PTCD), and 54 underwent bile duct stent implantation. One week later, total bilirubin (TB), direct bilirubin (DB), and alanine transaminase (ALT) were examined, and Child-Pugh scoring was conducted.38 of the patient underwent transcatheter arterial chemo-embolization (TACE). RESULTS: One week after drainage the levels of ALT, TB, and DB of the patients undergoing PTCD and stent implantation all decreased in comparison with those before the treatment, the levels of the stent implantation group being significantly lower than those of the PTCD group (P = 0.019, 0.002, and 0.002 respectively), but there was no significant difference in Child-Pugh scale between these 2 group (P = 0.396). One week after TACE the levels of TB, DB, and Child-Pugh scale of the TACE group were all significantly lower than those of the patients without TACE (P = 0.000, 0.002, and 0.002 respectively), however, there was no significant difference in ALT level between these 2 groups (P = 0.834). The cumulative mean survival time was 26.45 weeks [standard error (SE) 4.07], and the mean survival time of the PTCD group was 28.19 weeks (SE, 6.54), not significantly different from that of the stenting groups were [21.38 weeks (SE, 2.51), P = 0.713]. The mean survival time of the TACE group was 43.71 weeks (SE, 8.32), significantly longer than that of the patients without TACE [14.38 weeks (SE, 2.66), P = 0.000]. CONCLUSION: Stenting is more effective than PTCD on relieving jaundice when the decreasing extent of bilirubin level is concerned. TACE therapy following PTCD and stent implantation will significantly contribute to the survival time of MBO patients.