Purpose
To compare the efficacy and safety of transcatheter arterial chemoembolization (TACE) in combination with tyrosinkinase inhibitors (TKI) and PD-1 inhibitors, versus TACE monotherapy for the ...treatment of ruptured hepatocellular carcinoma (HCC).
Materials and Methods
This study included 104 patients with ruptured HCC receiving either combination therapy or TACE monotherapy at two centers between June 2015 and June 2022. Propensity score matching (PSM) analysis was used at a 1:2 ratio to reduce bias between the two groups. The primary outcome measures were overall survival (OS) and progression-free survival (PFS), and the secondary outcome measures were the occurrence of adverse events (AEs, Common Terminology Criteria for AEs, version 5.0.) and the peritoneal metastasis rate.
Results
A total of 69 patients were enrolled after PSM, including 23 patients in the combination group and 46 patients in the monotherapy group. The combination group exhibited a significantly longer median OS (553 days, 95% confidence interval CI 222.6–883.9) compared to the monotherapy group (105 days, 95% CI 81.2–128.7;
P
< 0.001). Similarly, the combination group showed a better median PFS (356 days, 95% CI 299.5–412.4) compared to the monotherapy group (97 days, 95% CI 75.9–118.1;
P
< 0.001). Moreover, there was no significant difference in the peritoneal metastasis rate (combination group: 8.6% vs. monotherapy group: 26.1%,
P
= 0.119). Grade 3 AEs occurred at a rate of 21.7% and 13% in combination and monotherapy groups, respectively. No Grade 4/5 AEs were observed in either group.
Conclusions
Our study demonstrated that the combination of TACE with TKI and PD-1 inhibitors significantly enhances OS and PFS compared to TACE monotherapy in ruptured HCC patients. Furthermore, this combined approach exhibited an acceptable safety profile.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Live-attenuated strain of measles virus (MV) has oncolytic effect. In this study, the antitumor effect of rMV-Hu191, a recombinant Chinese Hu191 MV generated in our laboratory by efficient reverse ...genetics system, was evaluated in gastric cancer (GC). From our data, rMV-Hu191 induced cytopathic effects and inhibited tumor proliferation both in vitro and in vivo by inducing caspase-dependent apoptosis. In mice bearing GC xenografts, tumor size was reduced and survival was prolonged significantly after intratumoral injections of rMV-Hu191. Furthermore, lipid rafts, a type of membrane microdomain with specific lipid compositions, played an important role in facilitating entry of rMV-Hu191. Integrity of lipid rafts was required for successful viral infection as well as subsequent cell apoptosis, but was not required for viral binding and replication. CD46, a MV membrane receptor, was found to be partially localized in lipid rafts microdomains. This is the first study to demonstrate that Chinese Hu191 MV vaccine strain could be used as a potentially effective therapeutic agent in GC treatment. As part of the underlying cellular mechanism, the integrity of lipid rafts is required for viral entry and to exercise the oncolytic effect.
•rMV-Hu191 induced cytopathic effects and inhibited tumor proliferation in vitro.•rMV-Hu191 suppressed tumors growth and prolonged survival in vivo.•rMV-Hu191 induced caspase-dependent apoptosis both in vitro and in vivo.•Lipid rafts mediated rMV-Hu191 entry, but not for virus binding and replication.•Lipid rafts is required for induction of caspase-dependent apoptosis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
BACKGROUNDThe thyroid-gut axis has a great influence on the maintenance of human health; however, we know very little about the effects of low-dose ionizing radiation (LDR) on thyroid hormone levels ...and gut microbiota composition. AIMTo investigate the potential effects of low-dose X-ray radiation to male C57BL/6J mice. METHODSPeripheral blood was collected for enzyme-linked immunosorbent assay (ELISA), and stool samples were taken for 16S ribosomal RNA (rRNA) gene sequencing after irradiation. RESULTSWe found that LDR caused changes in thyroid stimulating hormone (TSH) levels in the irradiated mice, suggesting a dose-dependent response in thyroid function to ionizing radiation. No changes in the diversity and richness of the gut microbiota were observed in the LDR-exposed group in comparison to the controls. The abundance of Moraxellaceae and Enterobacteriaceae decreased in the LDR-exposed groups compared with the controls, and the Lachnospiraceae abundance increased in a dose-dependent manner in the radiated groups. And the abundances of uncultured_bacterium_g_Acinetobacter, uncultured_bacterium_ o_Mollicutes_RF39, uncultured_bacterium_g_Citrobacter, and uncultured_ bacterium_g_Lactococcus decreased in the radiated groups at the genus level, which showed a correlation with radiation exposure and diagnostic efficacy. Analysis of functional metabolic pathways revealed that biological metabolism was predicted to have an effect on functional activities, such as nucleotide metabolism, carbohydrate metabolism, and glycan biosynthesis and metabolism. Furthermore, Kyoto Encyclopedia of Genes and Genomes pathway annotation also suggested that changes in the gut microbiota were related to processing functions, including translation, replication and repair. CONCLUSIONLDR can change thyroid function and the gut microbiota, and changes in the abundances of bacteria are correlated with the radiation dose.
Synthesizing hydroxy-functional linear copolymers with high molecular weights (
) and low branching degree (Den%) remains challenging, although there has been much headway in the area of functional ...copolymers. Here, we studied the effect of polymerization methods (one-step or two-step) and solvents (organic solvent: diphenyl ether or ionic liquids: C
mimTF
N/BF
/PF
,
= 2, 4, 6, 8, or 10) on
and Den% of copolymers P(OA-GA) (1,8-octanediol adipate (O-A)/glycerol adipate (G-A)). The
of P(OA-GA) reached up to 53 937 g mol
in two-step in diphenyl ether, and the Den% of glycerol can be controlled within 30%. The physical properties of these copolymers were investigated by contact angles, differential scanning calorimetry (DSC), and
biodegradation. With increasing glycerol content in the polyesters, both hydrophilic properties and degradation properties increased. This system not only facilitates the synthesis of functional polyesters with high molecular weight and low branching, but also expands the possibility of using bio-based monomers to synthesize functional polymers.
Hepatocellular carcinoma (HCC) is one of the deadliest malignant tumors that are harmful to human health. Increasing evidence has underscored the critical role of the competitive endogenous RNA ...(ceRNA) regulatory networks among various human cancers. However, the complexity and behavior characteristics of the ceRNA network in HCC were still unclear. In this study, we aimed to clarify a phosphatase and tensin homolog (PTEN)-related ceRNA regulatory network and identify potential prognostic markers associated with HCC. The expression profiles of three RNAs (long non-coding RNAs lncRNAs, microRNAs miRNAs, and mRNAs) were extracted from The Cancer Genome Atlas (TCGA) database. The DLEU2L-hsa-miR-100-5p/ hsa-miR-99a-5p-TAOK1 ceRNA network related to the prognosis of HCC was obtained by performing bioinformatics analysis. Importantly, we identified the DLEU2L/TAOK1 axis in the ceRNA by using correlation analysis, and it appeared to become a clinical prognostic model by Cox regression analysis. Furthermore, methylation analyses suggested that the abnormal upregulation of the DLEU2L/TAOK1 axis likely resulted from hypomethylation, and immune infiltration analysis showed that the DLEU2L/TAOK1 axis may have an impact on the changes in the tumor immune microenvironment and the development of HCC. In summary, the current study constructing a ceRNA-based DLEU2L/TAOK1 axis might be a novel important prognostic factor associated with the diagnosis and prognosis of HCC.
Display omitted
Shi et al. provide evidence that a ceRNA-based DLEU2L/TAOK1 axis has an impact on changes in the tumor immune microenvironment and might be a novel important prognostic factor associated with the diagnosis and prognosis of HCC.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Protein disulfide isomerase (PDI), a principal endoplasmic reticulum resident oxidoreductase chaperone, is known to play a role in malignancies. This study aims to explore the molecular mechanism by ...which PDI regulates endoplasmic reticulum stress and the apoptosis signaling pathway in colorectal cancer (CRC). We determined the expression of PDI in CRC tissues and adjacent normal tissues. Gain- and loss- of function assays were conducted to evaluate the effects of PDI on oxidative stress, endoplasmic reticulum stress, and apoptosis in CRC cells, as reflected by hydrogen peroxide (H2O2) level and the expression of related proteins. PDI protein expression was upregulated in CRC tissues. Small molecule inhibitor of PDI or PDI knockdown reduced CRC cell viability and induced apoptosis. Overexpression of wild-type PDI augmented the viability of CRC cells and inhibited endoplasmic reticulum stress response and apoptosis. Small molecule inhibitor of PDI or PDI knockdown increased intracellular H2O2 level and activated apoptosis signaling pathway, which could be reversed by wild-type PDI restoration. Moreover, the catalytic active site of C-terminal of PDI was found to be indispensable for the regulatory effects of PDI on H2O2 levels, apoptosis and cell viability in CRC cells. Collectively, PDI inhibits endoplasmic reticulum stress and apoptosis of CRC cells through its oxidoreductase activity, thereby promoting the malignancy of CRC.
•PDI is highly expressed in CRC.•PDI inhibits endoplasmic reticulum stress and apoptosis in CRC via reducing intracellular H2O2.•PDI activity negatively regulates endoplasmic reticulum stress and apoptosis in CRC cells.•The C-terminal catalytic active site of PDI protein inhibits endoplasmic reticulum stress and CRC cell apoptosis.•Inhibition of PDI oxidoreductase activity may be a new method for the treatment of CRC.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The study was designed to investigate whether the hamilton rating scale for depression (24-items) (HAM-D24) can be used to predict the diabetic microvascular complications in type 2 diabetes mellitus ...(T2DM) patients. 288 hospitalized patients with T2DM were enrolled. Their diabetic microvascular complications including diabetic nephropathy, diabetic retinopathy, diabetic peripheral neuropathy and diabetic foot as well as demographic, clinical data, blood samples and echocardiography were documented. All the enrolled patients received HAM-D24 evaluation. The HAM-D24 score and incidence of depression in T2DM patients with each diabetic microvascular complication were significantly higher than those in T2DM patients without each diabetic microvascular complication. After the adjustment of use of insulin and hypoglycemic drug, duration of T2DM, mean platelet volume, creatinine, albumin, fasting glucose, glycosylated hemoglobin type A1C, left ventricular ejection fraction, respectively, HAM-D24 score was still significantly associated with diabetic microvascular complications (OR = 1.188–1.281, all P < 0.001). The AUC of HAM-D24 score for the prediction of diabetic microvascular complication was 0.832 (0.761–0.902). 15 points of HAM-D24 score was considered as the optimal cutoff with the sensitivity of 0.778 and specificity of 0.785. In summary, HAM-D24 score may be used as a novel predictor of diabetic microvascular complications in T2DM patients.
•HAM-D24 scores could be used to predict the diabetic microvascular complication in T2DM patients (AUC of 0.832 (0.761–0.902).•15 points of HAM-D24 score was the optimal cutoff for the prediction of diabetic microvascular complications in T2DM patients (sensitivity of 0.778 and specificity of 0.785).•HAM-D24 score was significantly associated with diabetic microvascular complications after adjustments (OR = 1.188–1.281, all P < 0.001).
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Abstract
Background
Nonalcoholic fatty liver disease (NAFLD) is associated with disordered lipid and iron metabolism. Our previous study has substantiated the pivotal role of Caveolin-1 (Cav-1) in ...protecting hepatocytes and mediating iron metabolism in the liver. This study aimed to explore the specific mechanisms underlying the regulation of iron metabolism by Cav-1 in NAFLD.
Methods
Hepatocyte-specific
Cav-1
overexpression mice and knockout mice were used in this study.
Cav-1
-knockdown of RAW264.7 cells and mouse primary hepatocytes were performed to verify the changes in vitro. Moreover, a high-fat diet and palmitic acid plus oleic acid treatment were utilized to construct a NAFLD model in vivo and in vitro, respectively, while a high-iron diet was used to construct an in vivo iron overload model. Besides, iron concentration, the expression of Cav-1 and iron metabolism-related proteins in liver tissue or serum were detected using iron assay kit, Prussian blue staining, Western blotting, immunofluorescence staining, immunohistochemical staining and ELISA. The related indicators of lipid metabolism and oxidative stress were evaluated by the corresponding reagent kit and staining.
Results
Significant disorder of lipid and iron metabolism occurred in NAFLD. The expression of Cav-1 was decreased in NAFLD hepatocytes (
P
< 0.05), accompanied by iron metabolism disorder. Cav-1 enhanced the iron storage capacity of hepatocytes by activating the ferritin light chain/ferritin heavy chain pathway in NAFLD, subsequently alleviating the oxidative stress induced by excess ferrous ions in the liver. Further, CD68
+
CD163
+
macrophages expressing Cav-1 were found to accelerate iron accumulation in the liver, which was contrary to the effect of Cav-1 in hepatocytes. Positive correlations were also observed between the serum Cav-1 concentration and the serum iron-related protein levels in NAFLD patients and healthy volunteers (
P
< 0.05).
Conclusions
These findings confirm that Cav-1 is an essential target protein that regulates iron and lipid metabolic homeostasis. It is a pivotal molecule for predicting and protecting against the development of NAFLD.
Abstract
Circular RNA (circRNA) is a large class of covalently closed circRNA. As a member of competitive endogenous RNA, it participates in the regulation of circRNA-miRNA-mRNA network and plays an ...important role in the regulation of physiology and pathology. CircRNA is produced by the reverse splicing of exon, intron or both, forming exon or intron circRNA. Studies have shown that circRNA is a ubiquitous molecule, which exceeds the linear mRNA distributed in human cells. Because of its covalent closed-loop structure, circRNA is resistant to RNase R, which is more stable than linear mRNA; circRNA is highly conserved in different species. It was found that circRNA competitively adsorbs miRNA, as a miRNA sponge, to involve in the expression regulation of a variety of genes and plays an important role in tumor development, invasion, metastasis and other processes. These molecules offer new potential opportunities for therapeutic intervention and serve as biomarkers for diagnosis. In this paper, the origin, characteristics and functions of circRNA and its role in tumor development, invasion and metastasis, diagnosis and prognosis are reviewed.
The origin, characteristics and functions of circRNA and its role in tumor development, invasion and metastasis, diagnosis and prognosis are reviewed.
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