Comparison of drug-eluting bead with conventional transcatheter arterial chemoembolization for hepatocellular carcinoma with portal vein tumor thrombus: A randomized clinical trial.

BACKGROUND: Drug-eluting bead transarterial chemoembolization (DEB-TACE) has shown efficacy for treating hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). However, whether DEB-TACE is superior to conventional TACE (cTACE) remains unclear. OBJECTIVE: This randomized controlled trial aimed to compare the efficacy and safety of DEB-TACE versus cTACE in treating HCC with PVTT. METHODS: The study was conducted in a tertiary care center in Southeast China. HCC patients with PVTT were randomized at a 1:1 ratio to the DEB-TACE or cTACE groups. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were overall survival (OS) and incidence of adverse events (AEs). An independent review committee assessed the radiologic response according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST). AEs were assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Systemic therapies were not limited. RESULTS: Between September 2018, and July 2020, 163 patients were randomized to undergo DEB-TACE (n=82) or cTACE (n=81). Nine patients were excluded, and 154 patients were included in the final analysis; the median age was 55 years (range, 24-78 y), and 140 (90.9%) were male. The median PFS in the DEB-TACE group was 6.0 months (95% CI, 5.0 to 10.0) versus 4.0 months (95% CI, 3.0 to 5.0) in the cTACE group (hazard ratio, 0.63; 95% CI, 0.42 to 0.95; P=0.027). The DEB-TACE group showed a higher response rate (51[66.2%] vs. 36 [46.8%]; P=0.0015) and a longer median OS (12.0 months [95% CI, 9.0 to 16.0] vs. 8.0 months [95% CI, 7.0 to 11.0], P=0.039) than the cTACE group. Multivariate analysis showed that the treatment group, ALBI score, distant metastasis and additional TKIs were the four independent prognostic factors correlated with PFS. In addition, the treatment group, PVTT group and combined with surgery were independently correlated with OS. AEs were similar in the two groups, and postembolization syndrome was the most frequent AEs. CONCLUSION: DEB-TACE is superior to cTACE in treating HCC patients with PVTT due to the improved PFS and OS with an acceptable safety profile and may become a promising treatment strategy for HCC patients with PVTT. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1800018035.

Revealing the mechanism of quinoa on type 2 diabetes based on intestinal flora and taste pathways.

To investigate the antidiabetic effects and mechanisms of quinoa on type 2 diabetes mellitus (T2DM) mice model. In this context, we induced the T2DM mice model with a high-fat diet (HFD) combined with streptozotocin (STZ), followed by treatment with a quinoa diet. To explore the impact of quinoa on the intestinal flora, we predicted and validated its potential mechanism of hypoglycemic effect through network pharmacology, molecular docking, western blot, and immunohistochemistry (IHC). We found that quinoa could significantly improve abnormal glucolipid metabolism in T2DM mice. Further analysis showed that quinoa contributed to the improvement of gut microbiota composition positively. Moreover, it could downregulate the expression of TAS1R3 and TRPM5 in the colon. A total of 72 active components were identified by network pharmacology. Among them, TAS1R3 and TRPM5 were successfully docked with the core components of quinoa. These findings confirm that quinoa may exert hypoglycemic effects through gut microbiota and the TAS1R3/TRPM5 taste signaling pathway.

Coil and n-butyl-2-cyanoacrylate migration into the stomach after TIPS for gastroesophageal variceal bleeding: a case report and literature review.

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) is a well-established therapeutic option for the management of variceal hemorrhage in patients with cirrhosis. The simultaneous migration of the coil and n-butyl-2-cyanoacrylate (NBCA) is an extremely rare but significant complication after TIPS. Because of its rare presentation, there are currently no definitive recommendations for the management of this condition. CASE PRESENTATION: A 46-year-old man with hepatitis B cirrhosis underwent TIPS placement for uncontrolled gastroesophageal varix (GEV) bleeding secondary to portal hypertension in August 2018. During the procedure, large GEVs were embolized using a coil and NBCA. After a year, coil and NBCA migration into the stomach was observed. Attempts to remove the coil using biopsy forceps during esophagogastroduodenoscopy failed. The patient refused further intervention on the coil to prevent further complications and received conservative therapy instead. Close surveillance with endoscopy is recommended for detecting coils and varices. CONCLUSIONS: The present case reports an extremely rare but significant complication after TIPS, which highlights the management and follow-up recommendation for such rare complications. Our experience may provide guidance for the management of future similar cases and stimulate discussion about treatment methods of similar patients.

Comparison of Transjugular Intrahepatic Portosystemic Shunt in the Treatment of Cirrhosis With or Without Portal Vein Thrombosis: A Retrospective Study.

Aim: The purpose of our study was to conduct a retrospective analysis to compare the effectiveness of transjugular intrahepatic portosystemic shunts (TIPS) in the treatment of patients with cirrhosis with or without portal vein thrombosis (PVT). Methods: We included a total of 203 cirrhosis patients successfully treated with TIPS between January 2015 and January 2018, including 72 cirrhosis patients with PVT (35.5%) and 131 without PVT (64.5%). Our subjects were followed for at least 1 year after treatment with TIPS. Data were collected to estimate the mortality, shunt dysfunction, and complication rates after TIPS creation. Results: During the mean follow-up time of 19.5 ± 12.8 months, 21 (10.3%) patients died, 15 (7.4%) developed shunt dysfunction, and 44 (21.6%) experienced overt hepatic encephalopathy (OHE). No significant differences in mortality (P = 0.134), shunt dysfunction (P = 0.214), or OHE (P = 0.632) were noted between the groups. Age, model for end-stage liver disease (MELD) score, and refractory ascites requiring TIPS were risk factors for mortality. A history of diabetes, percutaneous transhepatic variceal embolization (PTVE), 8-mm diameter stent, and platelet (PLT) increased the risk of shunt dysfunction. The prevalence of variceal bleeding and recurrent ascites was comparable between the two groups (16.7 vs. 16.7% P = 0.998 and 2.7 vs. 3.8% P = 0.678, respectively). Conclusions: Transjugular intrahepatic portosystemic shunts are feasible in the management of cirrhosis with PVT. No significant differences in survival or shunt dysfunction were noted between the PVT and no-PVT groups. The risk of recurrent variceal bleeding, recurrent ascites, and OHE in the PVT group was generally similar to that in the no-PVT group. TIPS represents a potentially feasible treatment option in cirrhosis patients with PVT.

Safety and efficacy of drug-eluting bead transarterial chemoembolization with CalliSpheres® microsphere for hepatocellular carcinoma with portal vein tumor thrombus: a preliminary study.

Objective: To prospectively evaluate the safety and therapeutic effectiveness of drug-eluting beads transcatheter arterial chemoembolization (DEB-TACE) with CalliSpheres® microsphere (CSM) for the treatment of hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT), and to analyze the prognostic factors. Method: Between November 2015 and November 2017, consecutive 58 HCC patients with PVTT who received DEB-TACE with CSM treatment were prospectively enrolled in this study. The demographic characteristics, adverse events (AEs) and treatment response were collected. Overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan-Meier method. Univariate and multivariate Cox regression analyses were performed to determine the independent factors correlated with OS. Results: The objective response rate (ORR) was 79.3% in terms of tumors and 44.8% in thrombi. The median PFS and OS of patients were 5.0 months and 9.0 months respectively. The cumulative survival rate at 3-, 6-, 9-, 12-, 18- and 24-month were 94.8%, 72.4%, 53.4%, 41.4%, 22.4% and 19.0%, respectively. In a stepwise multivariate Cox proportional hazards model, the higher Child-Pugh classification (HR=2.279; 95%CI, 1.042-4.985, p = 0.039) and tumor burden (p = 0.008) were the significant predictors of poorer OS after adjustment for known risk factors. The most common clinical AEs were postembolization syndrome (PES) and the most prevalent laboratory toxicity was transient liver function damage. Conclusion: DEB-TACE with CSM is safe and well-tolerated in HCC patients with PVTT, and reveals a favorable preliminary clinical outcome. The higher Child-Pugh classification and liver tumor burden are independent prognostic factors associated with poor survival for HCC patients with PVTT treated by DEB-TACE with CSM.

Complete Response of Hepatocellular Carcinoma with Macroscopic Vascular Invasion and Pulmonary Metastasis to the Combination of Drug-Eluting Beads Transarterial Chemoembolization and Huaier Granule: A Case Report.

BACKGROUND: Hepatocellular carcinoma (HCC) associated with macroscopic vascular invasion and distant metastasis is an advanced-stage disease with an extremely poor prognosis and low survival rate. Therefore, there is an urgent need to develop novel therapeutic strategies to extend the lives of patients with advanced HCC. CASE PRESENTATION: We represent a case of HCC with macroscopic vascular invasion and pulmonary metastasis responding dramatically to the combination treatment with drug-eluting beads transarterial chemoembolization (DEB-TACE) and Huaier granule. A 64-year-old man with hepatitis B virus (HBV)-induced liver cirrhosis was diagnosed with advanced HCC involved renal vein and inferior vena cava accompanied by pulmonary metastasis. The patient received three cycles of on-demand DEB-TACE from 9th September 2016 to 22nd August 2017 and combined with Huaier granule 20 g three times a day orally. Eight months following the treatment, complete response occurred with regression of HCC and vascular thrombus and disappearance of pulmonary metastasis. The levels of AFP had decreased from 8165.8ng/mL to within the normal range (1.7 ng/mL). This is the first case report of complete response of HCC to the combination treatment with DEB-TACE and Huaier granule. At the most recent follow-up, he remained in remission 36 months after cessation of treatment without clinical or imaging evidence of disease recurrence. The current overall survival is 54 months since the initial treatment. CONCLUSION: Data from this clinical case report suggest that the combination treatment with DEB-TACE and Huaier granule is a promising therapeutic option for advanced HCC with macroscopic vascular invasion and distant metastasis.

Feasibility of computed tomography-guided irreversible electroporation for porcine kidney ablation.

OBJECTIVE: The objective was to evaluate the feasibility and safety of computed tomography (CT)-guided percutaneous irreversible electroporation (IRE) in porcine kidneys. MATERIALS AND METHODS: Under CT guidance, two monopole probes were used to precisely puncture through the renal parenchyma into the renal hilum in nine anesthetized adult Bama miniature pigs. After which, IRE ablation was performed. Biochemical and pathological examinations were carried out 2 h, 2, 7, and 14 days after the procedure. RESULTS: All procedures were performed successfully without any serious complications such as bleeding, infection, or death. All pigs survived until the end of the study. Pathological examinations showed that cells in the ablation area were dead within 2 days after the procedure, whereas the vascular endothelium showed only slight damage. After 2 days, endothelialization ensued and regrowth of smooth muscle cells was observed after 14 days. Hemogram tests indicated a transient increase but gradually returned to baseline levels 14 days after the procedure. CONCLUSION: IRE was essentially safe, however further studies on tumor ablation using several different animal models are needed.

Adjuvant Transarterial Chemoembolization for Barcelona Clinic Liver Cancer Stage A Hepatocellular Carcinoma After Hepatectomy.

INTRODUCTION: The care for patients with hepatocellular carcinoma (HCC) is challenging. This study is to evaluate the effect of adjuvant transarterial chemoembolization (TACE) for Barcelona Clinic Liver Cancer (BCLC) stage A HCC patients after hepatectomy. METHODS: Consecutive HCC patients with BCLC stage A, treated by hepatectomy alone (HA) or hepatectomy with TACE (HT), were retrospectively enrolled. Propensity score matching (PSM) was used to balance baseline differences. The recurrence-free survival (RFS) and overall survival (OS) were evaluated using the Kaplan-Meier. The impact of TACE on survival outcome was determined by Cox hazard regression. RESULTS: After PSM, 230 patients (115 HT and 115 HA) were enrolled in the analysis. The 1-, 3-, and 5-year RFS rates were 87.0, 63.5, and 50.4%, respectively, for the HT group, and 87.8, 67.0, and 58.3% for the HA group. The OS rates at 1-, 3-, and 5-year were 99.1, 93.9, and 87%, respectively, for the HT group, and 100, 92.2, and 88.7% for the HA group. No significant differences were seen in either the RFS (log-rank test, χ2 = 0.891, p = 0.345) or OS (log-rank test, χ2 = 0.146, p = 0.702) between the specific pairs of two groups. Cox regression identified that TACE was not the factor affecting RFS or OS (p = 0.399; HR 0.847; 95% CI 0.576-1.245 for RFS vs. p = 0.989; HR 0.995; 95% CI 0.471-2.100 for OS). CONCLUSION: Our data indicate that TACE is not an effective intervention in the adjuvant setting for BCLC stage A HCC after hepatectomy.

Drug-eluting beads transarterial chemoembolization with CalliSpheres microspheres for treatment of unresectable intrahepatic cholangiocarcinoma.

Objective: This study aimed to evaluate the efficacy and safety of doxorubicin-loaded drug-eluting beads transarterial chemoembolization (DEB-TACE) with CalliSpheres microspheres (CSM) in treating unresectable intrahepatic cholangiocarcinoma (ICC). Methods: 88 unresectable ICC patients who received DEB-TACE treatment with CSM were retrospectively enrolled in this study. Information about treatment response, survival and adverse events were collected. The Kaplan-Meier curve was used to evaluate progression-free survival (PFS) and overall survival (OS), and factors affecting OS were determined by Cox's proportional hazards regression model. Results: Tumor response of the whole sample of 88 patients was partial response (PR) in 58 (65.9%) patients, stable disease (SD) in 19 (21.6%) and progressive disease (PD) in 11 (12.5%) at one month after therapy, with no complete responses (CR). The median PFS and OS were 3.0 months and 9.0 months respectively. Cox's proportional hazards regression analysis disclosed that subsequent treatment was an independent favorable prognostic factor, while cholangiectasis, extensive intrahepatic tumor burden and extrahepatic metastasis were the three prognostic factors associated with poor survival in ICC patients. Besides, common adverse events included nausea/vomiting, abdominal pain and transient elevation of liver transaminase in patients treated by DEB-TACE with CSM. Conclusion: DEB-TACE with CSM is safe and well-tolerated for unresectable ICC patients, with a low complication rate and a relative benefit in terms of survival. Subsequent treatments including systemic/loco-regional treatments is an independent favorable prognostic factor, but cholangiectasis, extensive intrahepatic tumor burden and extrahepatic metastases are the three prognostic factors associated with poor survival.

Gene Therapy with Cytosine Deaminase and Endostatin Fusion Gene Mediated by Endothelial Progenitor Cells in Hepatomas.

PURPOSE: Gene-targeting therapy provides a novel therapeutic approach for tumor treatment using genetically modified endothelial progenitor cells (EPCs) as cellular carriers. This study applied EPCs armed with cytosine deaminase (CD) and endostatin (ES) fusion gene in liver cancer to explore its therapeutic effect. MATERIALS AND METHODS: EPCs from heart blood of male BALB/c nude mice were cultured and transfected with CD and ES fusion gene. Subsequently, these genetically modified cells were injected into mice bearing hepatoma through their tail veins. The tumor volumes and cell apoptosis were followed up. RESULTS: Tumor volume in the group injected CD/ES-EPCs greatly decreased. The positive rate of VEGF and CD31 in the tumor tissue was lowest in the CD/ES-EPC group. Furthermore, the number of apoptotic cells was highest in the CD/ES-EPC group. CONCLUSION: The EPCs transfected with CD/ES inhibited tumor growth and preferentially induced tumor cell apoptosis, providing a novel methodology for cancer-targeting therapy.

Circulating MicroRNAs in Plasma Decrease in Response to Sarcopenia in the Elderly.

sarcopenia has been defined as the aging-related disease with the declined mass, strength, and function of skeletal muscle, which is a major cause of morbidity and mortality in elders. Current diagnostic criteria of sarcopenia have not been agreed internationally, and the clinical diagnostic biomarkers for sarcopenia have not been identified. Circulating miRNAs (miRNAs, miRs) have recently been characterized as novel biomarkers for sarcopenia. However, the change of circulating miRNAs in response to sarcopenia are still not fully understood. Here, we enrolled a total of 93 elderly patients clinically diagnosed with sarcopenia and matching 93 non-sarcopenia elderly in this study. Specifically, levels of candidate circulating miRNAs which were involved in angiogenesis, inflammation and enriched in muscle and/or cardiac tissues were detected in these two groups. In small-sample screening experiments, plasma miR-155, miR-208b, miR-222, miR-210, miR-328, and miR-499 levels were significantly down-regulated in sarcopenia compared to those who non-sarcopenia. In contrast, miR-1, mir-133a, miR-133b, miR-21, miR-146a, miR-126, miR-221, and miR-20a were not changed significantly. Subsequently, we expanded the sample size to further detection and verification, and found that plasma miR-155, miR-208b, miR-222, miR-210, miR-328, and miR-499 levels in the sarcopenia group were significantly reduced compared to the non-sarcoma group, which is consistent with the results of the small-sample screening experiment. In addition, we showed that ASM/Height2, handgrip strength, knee extension and 4-meter velocity in sarcopenia group were significantly lower than those in non-sarcopenia group. Here we correlated the decrease of miR-208b, miR-499, miR-155, miR-222, miR-328, and miR-210 in sarcopenia group and non-sarcopenia group with diagnostic indexes of sarcopenia (ASM/Height2, Handgrip strength and 4-meter velocity) after adjusting sex. The results showed that miR-208b and miR-155 changes were significantly correlated with handgrip strength in woman, miR-208b, miR-499, and miR-222 changes were significantly correlated with ASM/Height2 in man, while other miRNAs changes did not show a strong correlation with these diagnostic indexes. In conclusion, plasma miR-208b, miR-499, miR-155, miR-222, miR-328, and miR-210 decrease in response to sarcopenia in the elderly. Although further studies are needed to clarify the potential use of circulating miRNAs as biomarkers of sarcopenia, present findings set the stage for defining circulating miRNAs as biomarkers and suggesting their physiological roles in elderly with sarcopenia.

[Toxic effects of Vitamin C combined with temozolomide on glioma cells and its mechanism].

Objective: To investigate the toxic effects of vitamin C (VC) combined with temozolomide (TMZ) on gliomas and its mechanism. Methods: Human glioma cells BMG-1 and SHG44 cells were cultured in vitro, specifically divided into control group (without VC and TMZ), TMZ group (0.2 mmol/L), VC (0.5 mmol/L)+TMZ(0.2 mmol/L) group and TMZ(0.2 mmol/L TMZ)+U0126(10 µmol/L)group, each experiment was repeated three times. Cell survival rate was detected by MTT assay; Cell apoptosis was detected by flow cytometry and Annexin V-FITC/PI staining; Reactive oxygen species (ROS) levels were detected by ROS detection kit, and Western blot was used to detect the expression levels of proteins related to apoptosis, autophagy and ERK pathway. Results: Compared with the control group, the survival rate of glioma cells in the TMZ group was decreased significantly(P＜0.05). Compared with the TMZ group, the survival rate of glioma cells in the VC+TMZ group was decreased significantly(P＜0.01), the cell apoptosis rate was increased, and the expressions of Bax, Cleaved caspase-3 and Cleaved PARP protein were increased, while the expression of Bcl-2 was decreased. The ROS level and autophagy rate were decreased, while the expression of LC3-II/LC3-1 was decreased, and the expression of p62 was increased in the VC+TMZ group (all P＜0.05). At the same time, VC combined with TMZ decreased the expression level of p-ERK1/2-related protein in BMG-1 and SHG44 cells, and increased the apoptosis rate (P＜0.05). Conclusion: VC combined with temozolomide can enhance the toxicity of glioma cells. This effect is to promote apoptosis and inhibit temozolomide-mediated autophagy through the regulation of the ERK signaling pathway.

Transfer of mitochondria from mesenchymal stem cells derived from induced pluripotent stem cells attenuates hypoxia-ischemia-induced mitochondrial dysfunction in PC12 cells.

Mitochondrial dysfunction in neurons has been implicated in hypoxia-ischemia-induced brain injury. Although mesenchymal stem cell therapy has emerged as a novel treatment for this pathology, the mechanisms are not fully understood. To address this issue, we first co-cultured 1.5 × 105 PC12 cells with mesenchymal stem cells that were derived from induced pluripotent stem cells at a ratio of 1:1, and then intervened with cobalt chloride (CoCl2) for 24 hours. Reactive oxygen species in PC12 cells was measured by Mito-sox. Mitochondrial membrane potential (?Ψm) in PC12 cells was determined by JC-1 staining. Apoptosis of PC12 cells was detected by terminal deoxynucleotidal transferase-mediated dUTP nick end-labeling staining. Mitochondrial morphology in PC12 cells was examined by transmission electron microscopy. Transfer of mitochondria from the mesenchymal stem cells derived from induced pluripotent stem cells to damaged PC12 cells was measured by flow cytometry. Mesenchymal stem cells were induced from pluripotent stem cells by lentivirus infection containing green fluorescent protein in mitochondria. Then they were co-cultured with PC12 cells in Transwell chambers and treated with CoCl2 for 24 hours to detect adenosine triphosphate level in PC12 cells. CoCl2-induced PC12 cell damage was dose-dependent. Co-culture with mesenchymal stem cells significantly reduced apoptosis and restored ?Ψm in the injured PC12 cells under CoCl2 challenge. Co-culture with mesenchymal stem cells ameliorated mitochondrial swelling, the disappearance of cristae, and chromatin margination in the injured PC12 cells. After direct co-culture, mitochondrial transfer from the mesenchymal stem cells stem cells to PC12 cells was detected via formed tunneling nanotubes between these two types of cells. The transfer efficiency was greatly enhanced in the presence of CoCl2. More importantly, inhibition of tunneling nanotubes partially abrogated the beneficial effects of mesenchymal stem cells on CoCl2-induced PC12 cell injury. Mesenchymal stem cells reduced CoCl2-induced PC12 cell injury and these effects were in part due to efficacious mitochondrial transfer.

Soluble Nogo receptor 1 fusion protein protects neural progenitor cells in rats with ischemic stroke.

Soluble Nogo66 receptor-Fc protein (sNgR-Fc) enhances axonal regeneration following central nervous system injury. However, the underlying mechanisms remain unclear. In this study, we investigated the effects of sNgR-Fc on the proliferation and differentiation of neural progenitor cells. The photothrombotic cortical injury model of ischemic stroke was produced in the parietal cortex of Sprague-Dawley rats. The rats with photothrombotic cortical injury were randomized to receive infusion of 400 µg/kg sNgR-Fc (sNgR-Fc group) or an equal volume of phosphate-buffered saline (photothrombotic cortical injury group) into the lateral ventricle for 3 days. The effects of sNgR-Fc on the proliferation and differentiation of endogenous neural progenitor cells were examined using BrdU staining. Neurological function was evaluated with the Morris water maze test. To further examine the effects of sNgR-Fc treatment on neural progenitor cells, photothrombotic cortical injury was produced in another group of rats that received transplantation of neural progenitor cells from the hippocampus of embryonic Sprague-Dawley rats. The animals were then given an infusion of phosphate-buffered saline (neural progenitor cells group) or sNgR-Fc (sNgR-Fc + neural progenitor cells group) into the lateral ventricle for 3 days. sNgR-Fc enhanced the proliferation of cultured neural progenitor cells in vitro as well as that of endogenous neural progenitor cells in vivo, compared with phosphate-buffered saline, and it also induced the differentiation of neural progenitor cells into neurons. Compared with the photothrombotic cortical injury group, escape latency in the Morris water maze and neurological severity score were greatly reduced, and distance traveled in the target quadrant was considerably increased in the sNgR-Fc group, indicating a substantial improvement in neurological function. Furthermore, compared with phosphate-buffered saline infusion, sNgR-Fc infusion strikingly improved the survival and differentiation of grafted neural progenitor cells. Our findings show that sNgR-Fc regulates neural progenitor cell proliferation, migration and differentiation. Therefore, sNgR-Fc is a potential novel therapy for stroke and neurodegenerative diseases, The protocols were approved by the Committee on the Use of Live Animals in Teaching and Research of the University of Hong Kong (approval No. 4560-17) in November, 2015.

Transcatheter embolization of hepatocellular carcinoma with epirubicin-loaded DC beads in Chinese patients.

BACKGROUND: This study evaluated the safety and efficacy of transcatheter chemoembolization with drug eluting beads (DEB-TACE) and compared it to the conventional TACE (cTACE) therapy method for hepatocellular carcinoma (HCC) in Chinese patients. METHODS: Seventy-four patients were treated with DEB-TACE using the DC bead, and 80 patients were treated with cTACE for HCC. The modified response evaluation criteria in solid tumors (mRECIST) criteria were used to evaluate clinical response, with adverse events assessed according to the Common Terminology Criteria for Adverse Events (CTCAE). RESULTS: Post-TACE, 9 patients (12.2%) achieved complete response (CR) and 44 (59.5%) achieved partial response (PR), with an overall tumor response rate (ORR) of 71.6% in the DEB-TACE group. Twelve patients (15%) achieved CR, and 38 (47.5%) achieved PR, with an ORR of 62.5% in the cTACE group. However, there was no significant difference in ORR between the two groups (P=0.229). Univariate logistic regression analysis determined that more than 3 nodules, higher Barcelona clinic liver cancer (BCLC) stage, portal vein invasion, previous chemotherapy (cTACE), and previous surgery were correlated with a worse ORR. Most common adverse events were not severe. CONCLUSIONS: DEB-TACE by DC bead was efficient and well-tolerated compared to cTACE in Chinese HCC patients. However, the present study showed no significant difference in ORR between the DEB-TACE and cTACE in the patient group with HCC. The BCLC stage, number of nodules, portal vein invasion, cTACE, and surgery history could possibly be a predictive factor for HCC treatment response.

Exendin-4 inhibits glioma cell migration, invasion and epithelial-to-mesenchymal transition through GLP-1R/sirt3 pathway.

GLP-1 analogue exendin-4, a glucagon-like peptide 1 receptor (GLP-1R) agonist which shares 53% sequence with GLP-1, plays an essential role in human tumors. However, the function and mechanisms underlying the effects of exendin-4 on glioma cell migration, invasion and epithelial-to-mesenchymal transition are still obscure. Firstly, we demonstrated that GLP-1R was expressed in all glioma cell lines including U87, U251, U373 and A172. Exendin-4 treatment inhibited glioma cell survival, proliferation, migration and invasion. Also, exendin-4 inhibited epithelial-to-mesenchymal transition through positively regulating the expression of E-cadherin (epithelial marker), and negatively regulating the level of Vimentin (mesenchymal marker). Interestingly, we next demonstrated that exendin-4 elevated sirt3 expression dependent on the high level of GLP-1R in U87 and 251 cells. Finally, we confirmed that depletion the level of GLP-1R or sirt3 both reversed the inhibitory action of exendin-4 on glioma cell migration and invasion. These findings demonstrate that exendin-4 treatment suppressed the migration and invasion of glioma cells through GLP-1R/sirt3 pathway and exendin-4 plays an inhibitory effect on glioblastoma cell migration and invasion.

Efficacy and safety profile of drug-eluting beads transarterial chemoembolization by CalliSpheres® beads in Chinese hepatocellular carcinoma patients.

BACKGROUND: This study aimed to investigate the efficacy and safety of drug eluting beads transarterial chemoembolization (DEB-TACE) treatment by CalliSpheres® in Chinese patients with hepatocellular carcinoma (HCC) as well as the predicting factors for response. METHODS: 99 patients with HCC were consecutively enrolled in this study. All participants were treated by CalliSpheres® DEB-TACE. Clinical response was evaluated according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria. Common Terminology Criteria for Adverse Events (CTCAE) was used to assess the adverse events and liver dysfunction during and after the operation. RESULTS: Post treatment, 16 patients (16.2%) achieved CR and 59 (59.6%) achieved PR, the ORR was 75.8%. Subgroup analysis showed that patients with higher BCLC stage were of worse CR and ORR rates, and the CR as well as ORR between patients with cTACE history and patients without cTACE history were similar. Univariate logistic regression analysis displayed that number of nodules > 3, higher BCLC stage and previous cTACE might be correlated with worse ORR but with no statistical significance. As to liver function, CTCAE grades of laboratory indexes for liver function were increased at 1 week compared to baseline and recovered to the baseline grades at 1-3 months post operation. Besides, most of the common adverse events were light and moderate in our study. CONCLUSIONS: In conclusion, DEB-TACE by CalliSpheres® was efficient and well tolerated in Chinese HCC patients, and BCLC stage, number of nodules and cTACE history were possibly correlated with treatment response.

Correction: Efficacy of transcatheter arterial chemoembolization for liver metastases arising from pancreatic cancer.

[This corrects the article DOI: 10.18632/oncotarget.14642.].

Correction: Post-pancreaticoduodenectomy hemorrhage: DSA diagnosis and endovascular treatment.

[This corrects the article DOI: 10.18632/oncotarget.17450.].

Effects of liver cirrhosis on portal vein embolization prior to right hepatectomy in patients with primary liver cancer.

Preoperative portal vein embolization (PVE) induces compensatory hyperplasia of the future liver remnants (FLR), thus increasing resectability in the non-cirrhotic patients with primary liver cancer (PLC). However, it is unclear if it is similar in patients with liver cirrhosis. Therefore, the present study investigated the PVE value prior to liver resection in patients with PLC, and the liver cirrhotic effects on the compensatory hypertrophy of FLRs following PVE. In the present study, 21 patients with PLC who successfully underwent hepatic resection subsequent to PVE, were retrospectively examined. The patients were divided into a non-cirrhosis group and a cirrhosis group according to the absence or presence of cirrhosis, respectively. The FLR volume between the two groups of patients was compared. There was a significant difference in the FLR volume for all patients prior to, and 4-6 weeks following, PVE (P<0.001). PVE induced significant compensatory hypertrophy in the FLRs whether in the non-cirrhosis group (P=0.002) or cirrhosis group (P<0.001). However, no significant difference was identified between the two groups with respect to FLR volume enlargement 4-6 weeks following PVE (P=0.373). In conclusion, PVE prior to hepatectomy may promote FLR compensatory hypertrophy and an increase in the resectability of PLC tumors. No significant effects of liver cirrhosis were identified on liver lobe hyperplasia following PVE.