Activated hepatic stellate cells promote hepatocellular carcinoma (HCC) progression. Hepatic stellate cells play a key role in retinoid metabolism, and activation of stellate cells increases retinoic ...acid (RA) in the liver. However, the role of RA in HCC proliferation remains unclear. We aimed to analyse the mechanism of RA in HCC proliferation. Thirty‐eight patients who had undergone hepatic resection for HCCs were recruited. Paired non‐tumour tissues, adjacent and distal to HCCs, were collected, and the RA levels in the tissues were analysed. The mechanisms of RA and HCC proliferation were assessed in liver cancer cell lines by protein and gene expression analyses. Early recurrence of HCC was significantly higher in patients with a higher RA concentration than in those with a lower RA concentration in tissues adjacent to HCCs (61.1% vs. 20%, p = .010). RA promoted HCC cell proliferation and activated the expression of Amphiregulin, a growth factor in hepatocarcinogenesis. The promoter of Amphiregulin contained the binding sites of the RA receptor, RXRα. Wnt signalling also activated the expression of Amphiregulin, and the RA and Wnt pathways acted synergistically to increase the expression of Amphiregulin. Furthermore, RXRα interacted with β‐catenin and then translocated to the nucleus to activate Amphiregulin. An increased RA concentration in the tissues adjacent to the tumour was associated with an early recurrence of HCC. RA activated the expression of Amphiregulin, and then promoted HCC proliferation, which might partly contribute to early recurrence of HCC after hepatic resection.
An increase in the concentration of retinoic acid (RA) in the microenvironment of hepatocellular carcinoma (HCC) is associated with a higher recurrence rate after the curative hepatic resection. Our work suggests that RA concentration could be used as a potential marker for early recurrence.
Beta-blockers can reduce recurrence, metastasis, and mortality in various cancers. In this study, we investigated the effect of propranolol, a non-selective beta-blocker on overall survival (OS) in ...unresectable/metastatic hepatocellular carcinoma (HCC) and on recurrence-free survival (RFS) in resectable, curable HCC.
Data were retrieved from the Taiwan National Health Insurance Research Database between January 2000 and December 2013. Propranolol users (for >1 year) and non-propranolol users were matched using a 1:2 propensity score in both cohorts.
The unresectable/metastatic HCC cohort comprised 1,560 propranolol users and 3,120 non-propranolol users (control group). On multivariate Cox regression analysis of HCC mortality, propranolol significantly reduced the mortality risk by 22% (hazard ratio HR = 0.78, 95% confidence interval CI 0.72-0.84, P <0.001). On stratified Cox regression analysis, propranolol also reduced the mortality risk in HCC patients with hepatitis B (HR = 0.92, 95% CI 0.85-0.99, P = 0.045), hepatitis C (HR = 0.85, 95% CI = 0.78-0.92, P = 0.001), liver cirrhosis (HR = 0.78, 95% CI = 0.72-0.85, P <0.001), and diabetes mellitus (HR = 0.87, 95% CI = 0.81-0.94, P = 0.008). The resectable, curable HCC cohort comprised 289 propranolol users and 578 non-propranolol users (control group), but there was no significant difference in RFS (P = 0.762) between propranolol and non-propranolol users.
This study revealed that propranolol could improve OS in unresectable/metastatic HCC.
Background
Aspiration pneumonia is the most common cause of death in patients who undergo percutaneous endoscopic gastrostomy (PEG). This study aims to evaluate the severity of oropharyngeal ...dysphagia and predict the risk of pneumonia in such patients, using upper gastrointestinal endoscopy.
Methods
Endoscope examined the pharyngolaryngeal region in patients who underwent PEG. The severity of oropharyngeal dysphagia was evaluated according to the amount and location of pooling of secretions in the pharyngolaryngeal region. Overall, 55 patients showed absent or minimal amount of secretions (control group), 10 patients showed moderate‐to‐large amounts of secretions filling the pyriform sinus (pharyngeal group), and 23 patients showed secretions entering the laryngeal vestibule (laryngeal group). Demographic data, swallowing level scale, and occurrence of pneumonia were recorded.
Results
The incidence of pneumonia was the highest in the pharyngeal group (70.0%), followed by that in the laryngeal (60.9%) and control groups (30.9%; P = 0.010). Multivariable regression showed that risk of pneumonia was significantly higher in the pharyngeal and laryngeal groups. Cumulative incidence rate of pneumonia was significantly higher in the laryngeal and pharyngeal groups than in the control group (log‐rank test, P = 0.001). Mortality rate was significantly higher in patients with suboptimal protective cough reflex than in others (50.0% vs 5.9%, P = 0.034).
Conclusion
Accumulation of abnormal amounts of secretions in the pyriform sinus or in the laryngeal vestibule increased the risk of the hospital admission following pneumonia in patients who underwent PEG. The mortality rate was higher in patients with suboptimal protective cough reflex.
Aspiration pneumonia is a major cause of death in patients on nasogastric tube (NGT) feeding. This study aimed to evaluate the oropharyngeal dysphagia and stratify risk of pneumonia in patients ...undergoing NGT feeding.
The study included patients on NGT feeding who underwent UGI endoscopy at Tri-Service General Hospital, Taiwan. Endoscopy was performed to examine the pharyngolaryngeal region. The severity of oropharyngeal dysphagia was evaluated according to the visualized amount and location of pooling of secretions in the pharyngolaryngeal region; 60 patients showed absent or minimal amount of secretions (control group), 14 patients showed moderate-to-large amounts of secretions filling the pyriform sinus (pharyngeal group), and 27 patients showed secretions entering the laryngeal vestibule (laryngeal group). Demographic data and occurrence of pneumonia were analyzed.
The incidence of pneumonia was highest in the pharyngeal group (4.2±3.6 episodes/person-years), followed by the laryngeal (2.6±2.2 episodes/ person-years) and control groups (1.7±3.8 episodes/person-years) (p=0.042). Multivariable regression showed significantly higher risk of pneumonia in the pharyngeal (adjusted odds ratio=2.7, 95% CI, 2.4-2.8, p<0.001) and laryngeal (adjusted odds ratio=2.0, 95% CI, 1.7-2.4, p<0.001) groups. The cumulative incidence rate of pneumonia was significantly higher in the laryngeal and pharyngeal groups than in the control group (log rank test, p<0.001).
Endoscopic pharyngolaryngeal observation can evaluate the oropharyngeal dysphagia. Visual evidence of oropharyngeal dysphagia increase the risk of pneumonia in patients on NGT feeding.
Aspiration pneumonia is the most common cause of death in patients with percutaneous endoscopic gastrostomy (PEG) and nasogastric tube (NGT) feeding. This study aimed to compare PEG versus NGT ...feeding regarding the risk of pneumonia, according to the severity of pooling secretions in the pharyngolaryngeal region.
Patients were stratified by endoscopic observation of the pooling secretions in the pharyngolaryngeal region: control group (<25% pooling secretions filling the pyriform sinus), pharyngeal group (25-100% pooling secretions filling the pyriform sinus), and laryngeal group (pooling secretions entering the laryngeal vestibule). Demographic data, swallowing level scale score, and pneumonia requiring hospital admission were recorded.
Patients with NGT (
= 97) had a significantly higher incidence of pneumonia (episodes/person-years) than those patients with PEG (
= 130) in the pharyngeal group (3.6 ± 1.0 vs. 2.3 ± 2.1,
< 0.001) and the laryngeal group (3.8 ± 0.5 vs. 2.3 ± 2.2 vs,
< 0.001). The risk of pneumonia was significantly higher in patients with NGT than in patients with PEG (adjusted hazard ratio = 2.85, 95% CI: 1.46-4.98,
< 0.001). Cumulative proportion of pneumonia was significantly higher in patients with NGT than with PEG for patients when combining the two groups (pharyngeal + laryngeal groups) (
= 0.035).
PEG is a better choice than NGT feeding due to the decrease in risk of pneumonia requiring hospital admission, particularly in patients with abnormal amounts of pooling secretions accumulation in the pyriform sinus or leak into the laryngeal vestibule.
Hepatocellular carcinoma (HCC) is a primary malignancy of the hepatocyte. Interleukin enhancer binding factor 2 (ILF2) plays a role in the development of HCC. However, the regulatory mechanisms of ...ILF2 expression in HCC remain unclear. In this study, we aimed to identify ILF2-targeting microRNAs (miRNAs) and to explore how they affect ILF2 expression in HCC.
The tissue specimens were collected from 25 HCC patients. The underlying regulatory mechanism of ILF2 expression in HCC progression was determined using luciferase reporter assay, quantitative real-time PCR, Western blotting, and BrdU incorporation assay.
Of predicted miRNA candidates (miR-122-5p, miR-425-5p, miR-136-5p, miR-7-5p, miR-421 and miR-543), a statistically significant inverse correlation by linear correlation analysis was observed between miR-136-5p and ILF2 mRNA expressions in patients with HCC (r = −0.627, P < 0.001). Further analysis demonstrated that ILF2 was directly regulated by miR-136-5p. In addition, we showed that long noncoding RNA colorectal neoplasia differentially expressed-h (lncRNA CRNDE-h) transcript expression was significantly up-regulated in HCC, and a miR-136-5p binding site was newly found in the lncRNA CRNDE-h transcript sequence using IntaRNA tool. In terms of mechanism, highly-expressed lncRNA CRNDE-h transcript can sponge miR-136-5p, thereby preventing it from interacting with target ILF2 mRNA while promoting the proliferation of HCC cells.
The lncRNA CRNDE-h/miR-136-5p/ILF2 axis plays a significant regulatory role in HCC progression, which may partly explain the pathogenic mechanisms of HCC and may provide promising potential targets for the diagnosis, treatment, and prognosis of HCC.
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During embryogenesis, the Activin/Nodal pathway promotes the mesendodermal lineage and inhibits neural fate. The molecular mechanisms underlying this role of the Activin/Nodal pathway are not clear. ...In this study, we report a role for protein tyrosine phosphatase 1B (PTP1B) in Activin-mediated early fate decisions during ESC differentiation and show that PTP1B acts as an effector of the Activin pathway to specify mesendodermal or neural fate. We found that the Activin/ALK4 pathway directly recruits PTP1B and stimulates its release from the endoplasmic reticulum through ALK4-mediated cleavage. Subsequently, PTP1B suppresses p-ERK1/2 signaling to inhibit neural specification and promote mesendodermal commitment. These findings suggest that a noncanonical Activin signaling pathway functions in lineage specification of mouse and human embryonic stem cells.
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•SB431542-mediated neural induction occurs via p-Erk(ERK)1/2 signaling•PTP1B, an effector of the Activin/Alk(ALK)4 pathway, regulates p-Erk(ERK)1/2•Activin-triggered PTP1B cleavage is mediated by Alk(ALK)4•PTP1B promotes mesendodermal fate and inhibits the neural lineage
A noncanonical Activin pathway promotes mesendodermal specification of mouse and human embryonic stem cells.
•The risk of liver abscess after DEB-TACE increased as treatment interval of DEB-TACE and ICIs was less than one month.•Though with higher incidence, liver abscess after DEB-TACE as in combination ...with ICIs didn’t show more aggressive course.•Receiving ICIs before DEB-TACE exhibited a trend toward liver abscess formation compared with receiving DEB-TACE before ICIs.
To analyze the safety of combination treatment comprising drug-eluting bead transarterial chemoembolization (DEB-TACE) and immune checkpoint inhibitors (ICIs) in hepatocellular carcinoma (HCC).
In total, 208 HCC patients receiving DEB-TACE were enrolled for this retrospective single-institution study. Among them, 50 patients who received ICIs at an interval less than one month from DEB-TACE were categorized into the DEB-ICI group; the remaining 158 patients were categorized into the DEB group. Albumin-bilirubin (ALBI) score before and at three months after DEB-TACE were recorded to evaluate liver function changes. Adverse events within three months after DEB-TACE were considered TACE-related and were compared between the two groups.
The DEB-ICI group had significantly higher incidence of liver abscess than the DEB group (14.0 % versus 5.1 %, p-value = 0.0337). No significant difference in the other TACE-related adverse events and change of ALBI score between the groups. Univariate logistic regression confirmed that combination with ICIs was an independent risk factor for liver abscess after DEB-TACE (odds ratio = 3.0523, 95 % confidence interval: 1.0474–8.8947, p-value = 0.0409); other parameters including subjective angiographic chemoembolization endpoint scale and combined targeted therapy were nonsignificant risk factors in this study population. In the DEB-ICI group, patients who received ICIs before DEB-TACE exhibited a trend toward liver abscess formation compared with those who received DEB-TACE before ICIs (23.8 % versus 6.9 %, p-value = 0.0922).
Combination treatment involving DEB-TACE and ICIs at an interval less than one month increased the risk of liver abscess after DEB-TACE. Greater caution is therefore warranted for HCC patients who receive ICIs and DEB-TACE with this short interval.
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