A CT Radiomics-Based Risk Score for Preoperative Estimation of Intraoperative Superior Mesenteric-Portal Vein Involvement in Pancreatic Ductal Adenocarcinoma.

BACKGROUND: The current radiologic criteria for assessing intraoperative superior mesenteric-portal vein (SMPV) involvement (i.e., presence of tumor-SMPV contact >180° or venous deformity) in pancreatic ductal adenocarcinoma (PDAC) are highly specific but insufficiently sensitive. Therefore, development of improved markers for a more accurate prediction is essential. This study aimed to develop a risk score model to estimate SMPV involvement in PDAC using radiomics analysis of computed tomography (CT) images. METHODS: Data from two institution-based cohorts of PDAC patients undergoing preoperative CT scans were used to develop (n = 173) and validate (n = 156) a radiomics-based risk score of SMPV involvement using clinical and imaging variables. A radiomics signature was developed based on 2436 radiomic features extracted from the semi-automatic three-dimensional segmentation ofn CT images. The SMPV involvement risk score was built using multivariate logistic regression and compared with the current radiologic criteria. RESULTS: The study surgically identified SMPV involvement in 59 (34.1%) and 57(36.5 %) patients with PDAC in the development and validation cohorts, respectively. A 12-feature-based radiomics signature achieved areas under receiver operating characteristics curves (AUCs) of 0.89 or greater for estimating SMPV involvement. Multivariate regression identified the radiomics signature and SMPV deformity as associated with SMPV involvement. The risk score model had significantly improved AUC (0.928 vs. 0.768; P < 0.001) and sensitivity (84.2% vs. 66.7%; P = 0.025) in the radiologic evaluation. CONCLUSIONS: The novel risk score in this study, combining radiomics signature and venous deformity, demonstrated promising performance for estimating SMPV involvement preoperatively for patients with PDAC.

Nomogram Estimating Vessels Encapsulating Tumor Clusters in Hepatocellular Carcinoma From Preoperative Gadoxetate Disodium-Enhanced MRI.

BACKGROUND: Vessels encapsulating tumor clusters (VETC) pattern is a novel microvascular pattern associated with poor outcomes of hepatocellular carcinoma (HCC). Preoperative estimation of VETC has potential to improve treatment decisions. PURPOSE: To develop and validate a nomogram based on gadoxetate disodium-enhanced MRI for estimating VETC in HCC and to evaluate whether the estimations are associated with recurrence after hepatic resection. STUDY TYPE: Retrospective. POPULATION: A total of 320 patients with HCC and histopathologic VETC pattern assessment from three centers (development cohort:validation cohort = 173:147). FIELD STRENGTH/SEQUENCE: A3.0  T/turbo spin-echo T2-weighted, spin-echo echo-planar diffusion-weighted, and 3D T1-weighted gradient-echo sequences. ASSESSMENT: A set of previously reported VETC- and/or prognosis-correlated qualitative and quantitative imaging features were assessed. Clinical and imaging variables were compared based on histopathologic VETC status to investigate factors indicating VETC pattern. A regression-based nomogram was then constructed using the significant factors for VETC pattern. The nomogram-estimated VETC stratification was assessed for its association with recurrence. STATISTICAL TESTS: Fisher exact test, t-test or Mann-Whitney test, logistic regression analyses, Harrell's concordance index (C-index), nomogram, Kaplan-Meier curves and log-rank tests. P value < 0.05 was considered statistically significant. RESULTS: Pathological VETC pattern presence was identified in 156 patients (development cohort:validation cohort = 83:73). Tumor size, presence of heterogeneous enhancement with septations or with irregular ring-like structures, and necrosis were significant factors for estimating VETC pattern. The nomogram incorporating these indicators showed good discrimination with a C-index of 0.870 (development cohort) and 0.862 (validation cohort). Significant differences in recurrence rates between the nomogram-estimated high-risk VETC group and low-risk VETC group were found (2-year recurrence rates, 50.7% vs. 30.3% and 49.6% vs. 31.8% in the development and validation cohorts, respectively). DATA CONCLUSION: The nomogram integrating gadoxetate disodium-enhanced MRI features was associated with VETC pattern preoperatively and with postoperative recurrence in patients with HCC. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.

Periodic Heterogeneous Surface with Superhydrophilic/Superhydrophobic Stripes Processed by a Picosecond Laser.

Heterogeneous surface with superhydrophilic/superhydrophobic stripes (HS-s/sS) has great practical significance, which can be used in fuel cell water management, condensation heat transfer enhancement, underwater drag reduction. Herein, a fast and simple method for uniform HS-s/sS on several mesh materials, including copper, stainless steel, and nickel, is achieved by using picosecond (ps) laser line-by-line scanning. Note that the scanning period between the lines is kept constant during processing, the HS-s/sS is formed by self-organized, while the similar structure cannot be processed on solid metal surfaces using the same parameters. The processing parameters, including scanning speed, defocus amount (DA), scanning period, and single pulse energy are systematically investigated to optimize HS-s/sS fabrication. It is found that the period of processed stripe on the mesh material is ∼1 mm, which is much larger than the scanning period. Interestingly, the as-prepared mesh surface show superhydrophobicity in the convex striped surface and superhydrophilicity in concave striped parts. The scanning electron microscopy results show that the structures on convex stripe are mainly composed of disordered hill-like structures, while the structures on the concave stripe mainly consist of periodic nanostripe structures. Moreover, the proportion of oxygen on the convex stripe is obviously higher than that on the concave stripe. The underlying mechanism of the HS-s/sS formation can be attributed to the interference between surface phonon polaritons (SPP) and the incident picosecond laser, as well as surface shock wave caused by the picosecond laser. We believe that such functional surfaces will be promising candidates for controlling liquid motion and fluid diversion processes.

Upregulation of ARHGAP30 attenuates pancreatic cancer progression by inactivating the ß-catenin pathway.

BACKGROUND: Pancreatic cancer is a highly malignant gastrointestinal cancer that can widely metastasize during the early stage of disease, and it is associated with one of the worst prognoses among cancers. In this study, we aimed to investigate the function of Rho GTPase-activating protein 30 (ARHGAP30) in pancreatic cancer cells and thus propose a novel therapy for pancreatic cancer. METHODS: ARHGAP30 expression in tumor tissues from patients with pancreatic cancer as well as cell lines was detected using immunohistochemistry (IHC), real-time polymerase chain reaction, and western blotting. Cell proliferation, transwell, and apoptosis assays were performed and the levels of related proteins were determined after ARHGAP30 knockdown or overexpression. Additionally, in vivo experiments were performed on nude mice. RESULTS: ARHGAP30 expression was found to be significantly increased in tumor tissues from patients with pancreatic cancer as well as in pancreatic cancer cell lines. IHC and prognostic analyses indicated that patients with high ARHGAP30 expression had a good prognosis. ARHGAP30 overexpression significantly decreased pancreatic cancer cell proliferation and metastasis; promoted apoptosis; reduced ß-catenin, B-cell lymphoma 2 (Bcl-2), matrix metalloproteinase-2 (MMP2), and MMP9 expression; and increased Bcl-2-associated X protein (Bax) and cleaved caspase-3 expression. ARHGAP30 knockdown elicited the opposite effects. The effects of ARHGAP30 knockdown were potently attenuated by the ß-catenin inhibitor XAV939. ARHGAP30 knockdown-induced RHOA activity was potently attenuated by the RHOA inhibitor CCG1423. In vivo, ARHGAP30 overexpression significantly inhibited lung metastasis in nude mice and increased the survival of mice with lung metastases. CONCLUSIONS: Our findings indicate that ARHGAP30 may function as a tumor suppressor in pancreatic cancer progression by regulating the expression of related genes and the ß-catenin pathway.

Study on mechanism about long noncoding RNA MALAT1 affecting pancreatic cancer by regulating Hippo-YAP signaling.

By investigating the migration and invasion ability in pancreatic cancer, this study probed into the lncRNA MALAT1 molecular mechanism on Hippo-YAP signaling. The expression of lncRNA MALAT1 in PC tissues and cells was detected by qRT-PCR and Western blot. The effect of si-MALAT1 on proliferation was determined by CCK-8 assay. Cell apoptosis, migration, and invasion were respectively detected by flow cytometry assay, wound healing assay, and transwell assay. Western blot and immunohistochemistry were successively used for detecting LATS1 and YAP1 expression in pancreatic cancer tissues. The microarray analysis determined that lncRNA MALAT1 in pancreatic cancer was highly expressed. LncRNA MALAT1 presented an extremely high expression level in pancreatic cancer tissues and cells. After transfected with si-MALAT1, the proliferation of AsPC-1 cells decreased, induce apoptosis of AsPC-1 cells, and migration and invasion ability were reduced. The tendency of LATS1 expression level was down-regulated and YAP1 show the opposite trend in the Hippo-YAP signaling. The in vivo assay was found that the tumor to be small in size and volume, and the expression of Ki-67 was decreased. High expression of lncRNA MALAT1 in PC disorder the proliferation, apoptosis, and migration and invasion ability via influence Hippo-YAP signaling pathway.

LncRNA UCA1 impacts cell proliferation, invasion, and migration of pancreatic cancer through regulating miR-96/FOXO3.

This study was expected to reveal the regulatory effects of lncRNA UCA1 on pancreatic cancer cell progression through targeting miR-96/FOXO3. Microarray analysis was carried out on 36 cases of pancreatic cancer tissues and 16 cases of adjacent tissues among them. Expression levels of lncRNA UCA1, miR-96, and FOXO3 in pancreatic cancer tissues and cell lines were determined by qRT-PCR. Expression levels of FOXO3 protein were determined by western blot. Cell viability, cell cycle and apoptosis, cell invasion and migration were detected by CCK-8, flow cytometry, and transwell assay, respectively. The colocalization relationship between lncRNA UCA1 and miR-96 was detected by RNA FISH. Whether UCA1 could target miR-96 and whether miR-96 could target FOXO3 3'UTR were verified by dual-luciferase reporter gene assay. High expression of lncRNA UCA1 and FOXO3 and low expression of miR-96 were shown in pancreatic cancer. Inhibition of UCA1 suppressed pancreatic tumor cell proliferation, colony formation, and metastasis, while inhibition of miR-96 promoted pancreatic cancer cell progression. FOXO3 was the downstream target gene of miR-96 and showed the opposite effects. LncRNA UCA1 promoted cell proliferation, invasion, migration and inhibited cell apoptosis of pancreatic cancer through down-regulating miR-96 and up-regulating FOXO3. © 2018 IUBMB Life, 70(4):276-290, 2018.

HMGB1-induced autophagy: a new pathway to maintain Treg function during chronic hepatitis B virus infection.

High-mobility group box-1 (HMGB1) protein, as one of the well-known damage-associated molecular pattern molecules (DAMPs), is enriched in chronic hepatitis B virus (HBV) infection and has a context-dependent role in autophagy, a highly conserved self-digestive process in response to environmental stress. Recent mouse studies indicate that autophagy is highly active in regulatory T (Treg)-cells. In the present study, we evaluated spontaneous and induced autophagy of peripheral Treg cells from 98 patients with chronic hepatitis B (CHB), by measuring levels of lipidated form of microtubule-associated light chain 3 (LC3-II, marker for closed autophagosomes) and observing autophagic vacuoles (AV) with transmission electron microscope. No significant difference was found in spontaneous autophagy of either Treg or CD4+ naive cells when comparing CHB patients with healthy subjects, apart from CHB-Treg showed significantly higher autophagic activity after activation by anti-CD3-CD28 beads. Besides, incubation of CHB-Treg cells with CHB-serum greatly maintained their autophagic behaviour, which could be significantly diminished by blocking HMGB1 with the neutralizing antibody. Further, we characterized time- and dose-dependent effects by recombinant HMGB1 protein on autophagy of CHB-Treg cells. We also documented a significant up-regulation of HMGB1 and its receptors [toll-like receptor (TLR4), receptor for advanced glycation end-product (RAGE)] in both peripheral and intra-hepatic microenvironments of CHB patients. Moreover, the RAGE-extracellular regulated protein kinases (ERK) axis and rapamycin-sensitive components of mammalian target of rapamycin (mTOR) pathways were demonstrated in vitro to be involved in HMGB1-induced autophagy of Treg cells. Additionally, HMGB1-induced autophagy could maintain cell survival and functional stability of CHB-Treg cells. Our findings could open new perspectives in developing therapeutic strategies to activate specific anti-HBV immunity by diminishing Treg autophagy.

HNF4A-AS1 inhibits the progression of hepatocellular carcinoma by promoting the ubiquitin-modulated degradation of PCBP2 and suppressing the stability of ARG2 mRNA.

Hepatocellular carcinoma (HCC) is a highly aggressive malignant tumor with a poor prognosis. Extensive research has revealed the significant role of long noncoding RNAs (lncRNAs) in the regulation of tumor development. In this study, high-throughput sequencing analysis was used to assess the expression levels of lncRNAs in three pairs of HCC tissues and their corresponding noncancerous tissues. Through quantitative real-time polymerase chain reaction (qRT-PCR) analysis and clinicopathological analysis, it was discovered that HNF4A-AS1 was downregulated in HCC tissues. Furthermore, its expression levels were found to be positively correlated with the prognosis of HCC patients. Subsequent in vitro and in vivo functional studies demonstrated that HNF4A-AS1 inhibits the proliferation, invasion, and stemness of HCC cells. Mechanistically, it was observed that HNF4A-AS1 physically interacts with the KH3 domain of PCBP2 through a specific segment (491-672 nt). This interaction facilitates the recruitment of PCBP2 by AIP4, leading to the ubiquitination and subsequent degradation of PCBP2. Furthermore, HNF4A-AS1 was found to regulate the stability of AGR2 mRNA by modulating PCBP2, thereby influencing the malignant phenotype of HCC. Overall, our study demonstrated a positive association between the decrease in HNF4A-AS1 expression and the prognosis of patients with HCC in a clinical setting. HNF4A-AS1 can suppress the stability of ARG2 mRNA by promoting the ubiquitin-modulated degradation of PCBP2, which suppresses HCC progression. HNF4A-AS1 may serve as a potential therapeutic target for HCC.

Exosomal SOX21-AS1 Regulates EREG by Sponging miR-451a and Promotes the Malignancy of Pancreatic Ductal Adenocarcinoma.

The incidence and mortality of pancreatic ductal adenocarcinoma (PDAC) have increased. Exosomes, as a regulatory mode of intercellular communication, contain lncRNAs. SOX21-AS1 has been studied in other cancers, and its expression is elevated in PDAC, but its role in PDAC remains unclear. First, we analyzed the expression of lncRNAs in PDAC tissues and nontumor tissues through the TCGA database. Next, the results of the RT-qPCR experiment confirmed the prediction that the expression of SOX21-AS1 was elevated in PDAC tissues. In vivo and in vitro cell function assays confirmed that the degree of malignancy of PDAC was proportional to the expression of SOX21-AS1. In addition, through exosome isolation and uptake experiments, we first found that PDAC could secrete exosomal SOX21-AS1 and play an angiogenic role in HUVECs. Subsequently, the relationship between SOX21-AS1, miR-451a and epiregulin (EREG) was verified through database prediction and analysis and RIP assays. Finally, functional recovery assays in vivo and in vitro verified that SOX21-AS1 regulates the expression of EREG through combination with miR-451a and thus promotes the malignancy of PDAC. SOX21-AS1 was upregulated in PDAC. The upregulation of SOX21-AS1 can stimulate the proliferation, migration, invasion, stemness and epithelial-mesenchymal transition (EMT) progression of PDAC cells. Furthermore, PDAC cells secrete exosomal SOX21-AS1, which is absorbed by HUVECs and promotes angiogenesis. Our study first identified that SOX21-AS1 promotes the malignancy of PDAC through the SOX21-AS1/miR-451a/EREG axis, and also that exosomal SOX21-AS1 promotes angiogenesis in PDAC.

Circ_0007386 Promotes the Progression of Hepatocellular Carcinoma Through the miR-507/ CCNT2 Axis.

Background: Circular RNAs (circRNAs) have been shown to play a crucial role in the initiation and development of Hepatocellular carcinoma (HCC). However, the mechanism and function of circ_0007386 in HCC are still unknown. Methods: Circ_0007386 expression level in HCC tissues, and HCC cell lines was further analyzed by qRT-PCR. Agarose gel electrophoresis and Sanger sequencing were used to figure out the structure of circ_0007386. The involvement of circ_0007386 in HCC development was evaluated by experimental investigations conducted in both laboratory settings (in vitro) and living organisms (in vivo). RNA immunoprecipitation, Western blotting, luciferase reporter assay and fluorescence in situ hybridization (FISH) were applied for finding out the interaction among circ_0007386, miR-507 and CCNT2. To assess the connection between circ_0007386 and lenvatinib resistance, lenvatinib-resistant HCC cell lines were employed. Results: The expression of circ_0007386 was found to increase in HCC tissues, and it was observed to be associated with a worse prognosis. Overexpression of circ_0007386 stimulated HCC cells proliferation, invasion, migration and the epithelial-mesenchymal transition (EMT) while silencing of circ_0007386 resulted in the opposite effect. Mechanistic investigations revealed that circ_0007386 acted as a competing endogenous RNA of miR-507 to prevent CCNT2 downregulation. Downregulating miR-507 or overexpressing CCNT2 could reverse phenotypic alterations that originated from inhibiting of circ_0007386. Importantly, circ_0007386 determines the resistance of hepatoma cells to lenvatinib treatment. Conclusion: Circ_0007386 advanced HCC progression and lenvatinib resistance through the miR-507/ CCNT2 axis. Meanwhile, circ_0007386 served as a potential biomarker and therapeutic target in HCC patients.

BAIAP2L2 promotes the malignancy of hepatocellular carcinoma via GABPB1-mediated reactive oxygen species imbalance.

Hepatocellular carcinoma (HCC) is a common type of cancer worldwide and ranks as the fourth leading cause of cancer-related deaths. This research investigation identified an upregulation of BAI1-associated protein 2-like 2 (BAIAP2L2) in HCC tissues, which was found to be an independent prognostic factor for overall survival in HCC patients. BAIAP2L2 was observed to enhance cell proliferation, metastasis, stemness, cell cycle progression, and inhibit apoptosis in HCC. Mechanistically, NFκB1 was found to stimulate BAIAP2L2 transcription by directly binding to its promoter region. BAIAP2L2 interacts with GABPB1 to inhibit its ubiquitin-mediated degradation and promote its nuclear translocation. BAIAP2L2 inhibits the levels of reactive oxygen species (ROS) by regulating GABPB1, thereby promoting cancer properties in HCC and reducing the sensitivity of HCC to lenvatinib. In summary, this study elucidates the role and underlying mechanism of BAIAP2L2 in HCC, providing a potential biomarker and therapeutic target for this disease.

Biomimicking covalent organic frameworks nanocomposite coating for integrated enhanced anticorrosion and antifouling properties of a biodegradable magnesium stent.

The utilization of biodegradable magnesium (Mg) alloys in the fabrication of temporary non-vascular stents is an innovative trend in biomedical engineering. However, the heterogeneous degradation profiles of these biomaterials, together with potential bacterial colonization that could precipitate infectious or stenotic complications, are critical obstacles precluding their widespread clinical application. In pursuit of overcoming these limitations, this study applies the principles of biomimicry, particularly the hydrophobic and anti-fouling characteristics of lotus leaves, to pioneer the creation of nanocomposite coatings. These coatings integrate poly-trimethylene carbonate (PTMC) with covalent organic frameworks (COFs), to modify the stent's surface property. The strategic design of the coating's topography, porosity, and self-polishing capabilities collectively aims to decelerate degradation processes and minimize biological adhesion. The protective qualities of the coatings were substantiated through rigorous testing in both in vitro dynamic bile tests and in vivo New Zealand rabbit choledochal models. Empirical findings from these trials confirmed that the implementation of COF-based nanocomposite coatings robustly fortifies Mg implantations, conferring heightened resistance to both biocorrosion and biofouling as well as improved biocompatibility within bodily environments. The outcomes of this research elucidate a comprehensive framework for the multifaceted strategies against stent corrosion and fouling, thereby charting a visionary pathway toward the systematic conception of a new class of reliable COF-derived surface modifications poised to amplify the efficacy of Mg-based stents. STATEMENT OF SIGNIFICANCE: Biodegradable magnesium (Mg) alloys are widely utilized in temporary stents, though their rapid degradation and susceptibility to bacterial infection pose significant challenges. Our research has developed a nanocomposite coating inspired by the lotus, integrating poly-trimethylene carbonate with covalent organic frameworks (COF). The coating achieved self-polishing property and optimal surface energy on the Mg substrate, which decelerates stent degradation and reduces biofilm formation. Comprehensive evaluations utilizing dynamic bile simulations and implantation in New Zealand rabbit choledochal models reveal that the coating improves the durability and longevity of the stent. The implications of these findings suggest the potential COF-based Mg alloy stent surface treatments and a leap forward in advancing stent performance and endurance in clinical applications.

Corrigendum to 'Predicting post-resection recurrence by integrating imaging-based surrogates of distinct vascular patterns of hepatocellular carcinoma' (JHEP Reports 5 [2023] 100806).

[This corrects the article DOI: 10.1016/j.jhepr.2023.100806.].

Cholecystectomy Significantly Alters Gut Microbiota Homeostasis and Metabolic Profiles: A Cross-Sectional Study.

Cholecystectomy (CCE) is a standard clinical treatment for conditions like gallstones and cholecystitis. However, its link to post-CCE syndrome, colorectal cancer, and nonalcoholic fatty liver disease has raised concerns. Additionally, studies have demonstrated the disruptive effects of CCE on gut microbiota homeostasis and bile acid (BA) metabolism. Considering the role of gut microbiota in regulating host metabolic and immune pathways, the use of dietary and probiotic intervention strategies to maintain a stable gut ecosystem after CCE could potentially reduce associated disease risks. Inter-study variations have made it challenging to identify consistent gut microbiota patterns after CCE, a prerequisite for targeted interventions. In this study, we first meta-analyzed 218 raw 16S rRNA gene sequencing datasets to determine consistent patterns of structural and functional changes in the gut microbiota after CCE. Our results revealed significant alterations in the gut microbiota's structure and function due to CCE. Furthermore, we identified characteristic gut microbiota changes associated with CCE by constructing a random model classifier. In the validation cohort, this classifier achieved an area under the receiver operating characteristic curve (AUC) of 0.713 and 0.683 when distinguishing between the microbiota of the CCE and healthy groups at the family and genus levels, respectively. Further, fecal metabolomics analysis demonstrated that CCE also substantially modified the metabolic profile, including decreased fecal short-chain fatty acid levels and disrupted BA metabolism. Importantly, dietary patterns, particularly excessive fat and total energy intake, influenced gut microbiota and metabolic profile changes post-CCE. These dietary habits were associated with further enrichment of the microbiota related to BA metabolism and increased levels of intestinal inflammation after CCE. In conclusion, our study identified specific alterations in gut microbiota homeostasis and metabolic profiles associated with CCE. It also revealed a potential link between dietary patterns and gut microbiota changes following CCE. Our study provides a theoretical basis for modulating gut microbiota homeostasis after CCE using long-term dietary strategies and probiotic interventions.

Exosome-transported circHDAC1_004 Promotes Proliferation, Migration, and Angiogenesis of Hepatocellular Carcinoma by the miR-361-3p/NACC1 Axis.

Background and Aims: Hepatocellular carcinoma (HCC) is among the most common malignant tumors globally. Circular RNAs (circRNAs), as a type of noncoding RNAs, reportedly participate in various tumor biological processes. However, the role of circHDAC1_004 in HCC remains unclear. Thus, we aimed to explore the role and the underlying mechanisms of circHDAC1_004 in the development and progression of HCC. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect circHDAC1_004 expression (circ_0005339) in HCC. Sanger sequencing and agarose gel electrophoresis were used to determine the structure of circHDAC1_004. In vitro and in vivo experiments were used to determine the biological function of circHDAC1_004 in HCC. Herein, qRT-PCR, RNA immunoprecipitation, western blotting, and a luciferase reporter assay were used to explore the relationships among circHDAC1_004, miR-361-3p, and NACC1. Results: circHDAC1_004 was upregulated in HCC and significantly associated with poor overall survival. circHDAC1_004 promoted HCC cell proliferation, stemness, migration, and invasion. In addition, circHDAC1_004 upregulated human umbilical vein endothelial cells (HUVECs) and promoted angiogenesis through exosomes. circHDAC1_004 promoted NACC1 expression and stimulated the epithelial-mesenchymal transition pathway by sponging miR-361-3p. Conclusions: We found that circHDAC1_004 overexpression enhanced the proliferation, stemness, and metastasis of HCC via the miR-361-3p/NACC1 axis and promoted HCC angiogenesis through exosomes. Our findings may help develop a possible therapeutic strategy for HCC.

Predicting post-resection recurrence by integrating imaging-based surrogates of distinct vascular patterns of hepatocellular carcinoma.

Background & Aims: Distinct vascular patterns, including microvascular invasion (MVI) and vessels encapsulating tumour clusters (VETC), are associated with poor outcomes of hepatocellular carcinoma (HCC). Imaging surrogates of these vascular patterns potentially help to predict post-resection recurrence. Herein, a prognostic model integrating imaging-based surrogates of these distinct vascular patterns was developed to predict postoperative recurrence-free survival (RFS) in patients with HCC. Methods: Clinico-radiological data of 1,285 patients with HCC from China undergoing surgical resection were retrospectively enrolled from seven medical centres between 2014 and 2020. A prognostic model using clinical data and imaging-based surrogates of MVI and VETC patterns was developed (n = 297) and externally validated (n = 373) to predict RFS. The surrogates (i.e. MVI and VETC scores) were individually built from preoperative computed tomography using two independent cohorts (n = 360 and 255). Whether the model's stratification was associated with postoperative recurrence following anatomic resection was also evaluated. Results: The MVI and VETC scores demonstrated effective performance in their respective training and validation cohorts (AUC: 0.851-0.883 for MVI and 0.834-0.844 for VETC). The prognostic model incorporating serum alpha-foetoprotein, tumour multiplicity, MVI score, and VETC score achieved a C-index of 0.748-0.764 for the developing and external validation cohorts and generated three prognostically distinct strata. For patients at model-predicted medium risk, anatomic resection was associated with improved RFS (p <0.05). By contrast, anatomic resection had no impact on RFS in patients at model-predicted low or high risk (both p >0.05). Conclusions: The proposed model integrating imaging-based surrogates of distinct vascular patterns enabled accurate prediction for RFS. It can potentially be used to identify HCC surgical candidates who may benefit from anatomic resection. Impact and implications: MVI and VETC are distinct vascular patterns of HCC associated with aggressive biological behaviour and poor outcomes. Our multicentre study provided a model incorporating imaging-based surrogates of these patterns for preoperatively predicting RFS. The proposed model, which uses imaging detection to estimate the risk of MVI and VETC, offers an opportunity to help shed light on the association between tumour aggressiveness and prognosis and to support the selection of the appropriate type of surgical resection.

Activatable UCL/CT/MR-enhanced in vivo imaging-guided radiotherapy and photothermal therapy.

Although sophisticated radiotherapy (RT) technology has been widely applied in clinical oncotherapy, unsatisfactory therapeutic effects due to hypoxic tumor microenvironments and complications are still prevalent. Herein, copper sulphide nanoparticles (CuS NPs) wrapped on the surface of upconversion nanoparticles (UCNPs) via manganese dioxide (MnO2) coatings were synthesized for O2 self-supplementing and enhanced combinational RT/photothermal therapy (PTT). In our design, the nanoplatforms can be rapidly enriched at tumor sites by the enhanced permeability and retention (EPR) effect and respond to the tumor microenvironment. The surface MnO2 coatings can interact with over-expressed H2O2 in tumors and cause an abundant generation of oxygen for hypoxic improvement, leading to an enhanced RT. More importantly, by irradiation with near-infrared light, the scattered CuS NPs can convert light energy into heat to destroy tumor cells and reinforce the therapeutic effects of RT. Furthermore, these NPs also displayed excellent performances in upconversion fluorescence imaging (UCL), computerized tomographic (CT) scanning and magnetic resonance imaging (MRI), demonstrating a potential imaging-guided cancer therapy system.

LncRNA TTN-AS1 intensifies sorafenib resistance in hepatocellular carcinoma by sponging miR-16-5p and upregulation of cyclin E1.

Drug resistance has always been an important problem affecting the therapeutic effect of hepatocellular carcinoma (HCC). To investigate the potential role of lncRNA TTN-AS1 in HCC cells with sorafenib (SOR) resistance, and explore the underlying pathways, quantitative real time polymerase chain reaction (qRT-PCR) was used to test the expression of TTN-AS1 in HCC tissues and cells. Then, the expression of TTN-AS1 was down-regulated by shRNA, the activity changes, apoptosis and related protein expression in HCC cells with/without SOR treatment were observed in succession. Expression levels of the downstream target of TTN-AS1, miR-16-5p were studied by dual-luciferase binding assay, cell proliferation, and western blotting analysis. Nude mice models of human HCC with TTN-AS1 gene knockdown were established to observe the tumor growth. As the results revealed, TTN-AS1 silencing in HCC cells induced apoptosis by enhancing the sensitivity of cells to SOR, and the tumor in nude mice became smaller. The mechanism study showed that miR-16-5p was affected by TTN-AS1 sponge, up-regulated cyclin E1 expression, and regulated PTEN/Akt signaling pathway, thereby significantly alleviating the inhibition of apoptosis of HCC cells induced by TTN-AS1 gene. Collectively, our results provided TTN-AS1 as a potential therapeutic target for sorafenib resistance in HCC.