Apigenin inhibits tumor angiogenesis by hindering microvesicle biogenesis via ARHGEF1.

Extracellular vesicles are essential for intercellular communication and are involved in tumor progression. Inhibiting the direct release of extracellular vesicles seems to be an effective strategy in inhibiting tumor progression, but lacks of investigation. Here, we report a natural flavonoid compound, apigenin, could significantly inhibit the growth of hepatocellular carcinoma by preventing microvesicle secretion. Mechanistically, apigenin primarily targets the guanine nucleotide exchange factor ARHGEF1, inhibiting the activity of small G protein Cdc42, which is essential in regulating the release of microvesicles from tumor cells. In turn, this inhibits tumor angiogenesis related to VEGF90K transported on microvesicles, ultimately impeding tumor progression. Collectively, these findings highlight the therapeutic potential of apigenin and shed light on its anticancer mechanisms through inhibiting microvesicle biogenesis, providing a solid foundation for the refinement and practical application of apigenin.

Elevated SLC1A5 associated with poor prognosis and therapeutic resistance to transarterial chemoembolization in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a common malignant tumor, and glutamine is vital for tumor cells. The role of glutamine transporter SLC1A5 in tumor progression and transarterial chemoembolization (TACE) efficacy is under study. This research seeks to determine the impact of SLC1A5 expression on the prognosis and TACE efficacy of HCC and elucidate its mechanisms. METHODS: SLC1A5 expression in HCC, correlation with patient outcomes, and response to TACE were studied in an open access liver cancer dataset and confirmed in our cohort. Additionally, the correlation between SLC1A5 expression and hypoxia, angiogenesis and immune infiltration was analyzed and verified by immunohistochemistry, immunofluorescence and transcriptome sequencing. Liver cancer cell lines with SLC1A5 expression knockdown or overexpression were constructed, and cell proliferation, colony formation, apoptosis, migration and drug sensitivity as well as in vivo xenograft tumor were measured. A gene set enrichment analysis was conducted to determine the signaling pathway influenced by SLC1A5, and a western blot analysis was performed to detect protein expression alterations. RESULTS: SLC1A5 expression was higher in HCC tissue and associated with poor survival and TACE resistance. Hypoxia could stimulate the upregulation of glutamine transport, angiogenesis and SLC1A5 expression. The SLC1A5 expression was positively correlated with hypoxia and angiogenesis-related genes, immune checkpoint pathways, macrophage, Tregs, and other immunosuppressive cells infiltration. Knockdown of SLC1A5 decreased proliferation, colony formation, and migration, but increased apoptosis and increased sensitivity to chemotherapy drugs. Downregulation of SLC1A5 resulted in a decrease in Vimentin and N-cadherin expression, yet an increase in E-cadherin expression. Upregulation of SLC1A5 increased Vimentin and N-cadherin expression, while decreasing E-cadherin. Overexpression of ß-catenin in SLC1A5-knockdown HCC cell lines could augment Vimentin and N-cadherin expression, suppress E-cadherin expression, and increase the migration and drug resistance. CONCLUSIONS: Elevated SLC1A5 was linked to TACE resistance and survival shortening in HCC patients. SLC1A5 was positively correlated with hypoxia, angiogenesis, and immunosuppression. SLC1A5 may mediate HCC cell migration and drug resistance via Epithelial-mesenchymal transition (EMT) pathway.

[The influence of knocking down the expression of low-density lipoprotein receptor associated proteins on the vascular abnormalities in hepatocellular carcinoma and its mechanisms].

Objectives: To investigate the effect of the expression of low-density lipoprotein receptor associated protein (LDLR) on the vascular abnormalities in hepatocellular carcinoma (HCC) and its mechanisms. Methods: Based on the information of Oncomine Cancer GeneChip database, we analyzed the correlation between the expression level of LDLR and the expression level of carcinoembryonic antigen (CEA) and CD31 in hepatocellular carcinoma tissues. Lentiviral transfection of short hairpin RNA target genes was used to construct LDLR-knockdown MHCC-97H and HLE hepatocellular carcinoma cells. The differential genes and their expression level changes in LDLR-knockdown hepatocellular carcinoma cells were detected by transcriptome sequencing, real-time fluorescence quantitative polymerase chain reaction, and protein immunoblotting. The gene-related signaling pathways that involve LDLR were clarified by enrichment analysis. The effect of LDLR on CEA was assessed by the detection of CEA content in conditioned medium of hepatocellular carcinoma cells. Angiogenesis assay was used to detect the effect of LDLR on the angiogenic capacity of human umbilical vein endothelial cells, as well as the role of CEA in the regulation of angiogenesis by LDLR. Immunohistochemical staining was used to detect the expression levels of LDLR in 176 hepatocellular carcinoma tissues, and CEA and CD31 in 146 hepatocellular carcinoma tissues, and analyze the correlations between the expression levels of LDLR, CEA, and CD31 in the tissues, serum CEA, and alanine transaminase (ALT). Results: Oncomine database analysis showed that the expressions of LDLR and CEA in the tissues of hepatocellular carcinoma patients with portal vein metastasis were negatively correlated (r=-0.64, P=0.001), whereas the expressions of CEA and CD31 in these tissues were positively correlated ( r=0.46, P=0.010). The transcriptome sequencing results showed that there were a total of 1 032 differentially expressed genes in the LDLR-knockdown group and the control group of MHCC-97H cells, of which 517 genes were up-regulated and 515 genes were down-regulated. The transcript expression level of CEACAM5 was significantly up-regulated in the cells of the LDLR-knockdown group. The Gene Ontology (GO) function enrichment analysis showed that the differential genes were most obviously enriched in the angiogenesis function. The Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analysis showed that the relevant pathways involved mainly included the cellular adhesion patch, the extracellular matrix receptor interactions, and the interactions with the extracellular matrix receptors. The CEA content in the conditioned medium of the LDLR-knockdown group was 43.75±8.43, which was higher than that of the control group (1.15±0.14, P＜0.001). The results of angiogenesis experiments showed that at 5 h, the number of main junctions, the number of main segments, and the total area of the lattice formed by HUVEC cells cultured with the conditioned medium of MHCC-97H cells in the LDLR-knockdown group were 295.3±26.4, 552.5±63.8, and 2 239 781.0±13 8211.9 square pixels, which were higher than those of the control group (113.3±23.5, 194.8±36.5, and 660 621.0±280 328.3 square pixels, respectively, all P＜0.01).The number of vascular major junctions, the number of major segments, and the total area of the lattice formed by HUVEC cells cultured in conditioned medium with HLE cells in the LDLR-knockdown group were 245.3±42.4, 257.5±20.4, and 2 535 754.5±249 094.2 square pixels, respectively, which were all higher than those of the control group (113.3±23.5, 114.3±12.2, and 1 565 456.5±219 259.7 square pixels, respectively, all P＜0.01). In the conditioned medium for the control group of MHCC-97H cells,the number of main junctions, the number of main segments, and the total area of the lattice formed by the addition of CEA to cultured HUVEC cells were 178.9±12.0, 286.9±12.3, and 1 966 990.0±126 249.5 spixels, which were higher than those in the control group (119.7±22.1, 202.7±33.7, and 1 421 191.0±189 837.8 square pixels, respectively). The expression of LDLR in hepatocellular carcinoma tissues was not correlated with the expression of CEA, but was negatively correlated with the expression of CD31 (r=-0.167, P=0.044), the level of serum CEA (r=-0.061, P=0.032), and the level of serum ALT(r=-0.147,P=0.05). The expression of CEA in hepatocellular carcinoma tissues was positively correlated with the expression of CD31 (r=0.192, P=0.020). The level of serum CEA was positively correlated with the level of serum ALT (r=0.164, P=0.029). Conclusion: Knocking down LDLR can promote vascular abnormalities in HCC by releasing CEA.

20(S)-Ginsenoside Rh2 inhibits hepatocellular carcinoma by suppressing angiogenesis and the GPC3-mediated Wnt/ß­catenin signaling pathway.

20(S)-Ginsenoside Rh2 has significant anti-tumor effects in various types of cancers, including human hepatocellular carcinoma (HCC). However, its molecular targets and mechanisms of action remain largely unknown. Here, we aim to elucidate the potential mechanisms by which Rh2 suppresses HCC growth. We first demonstrate the role of Rh2 in inhibiting angiogenesis. We observe that Rh2 effectively suppresses cell proliferation and induces apoptosis in HUVECs. Furthermore, Rh2 significantly inhibits HepG2-stimulated HUVEC proliferation, migration and tube formation, accompanied by the downregulation of VEGF and MMP-2 expressions. We also reveal that Rh2 inhibits HCC growth through the downregulation of glypican-3-mediated activation of the Wnt/ß-catenin pathway. We observe a dose-dependent inhibition of proliferation and induction of apoptosis in HepG2 cells upon Rh2 treatment, which is mediated by the inhibition of glypican-3/Wnt/ß-catenin signaling. Moreover, downregulation of glypican-3 expression enhances the effects of Rh2 on the glypican-3/Wnt/ß-catenin signaling pathway, resulting in greater suppression of tumor growth in HepG2 cells. Collectively, our findings shed light on the molecular mechanisms through which Rh2 modulates HCC growth, which involve the regulation of angiogenesis and the glypican-3/Wnt/ß-catenin pathway. These insights may pave the way for the development of novel therapeutic strategies targeting these pathways for the treatment of HCC.

Two-dimensional perfusion angiography permits direct visualization of redistribution of flow in hepatocellular carcinoma during b-TACE.

OBJECTIVES: To demonstrate in vivo redistribution of the blood flow towards HCC's lesions by utilizing two-dimensional perfusion angiography in b-TACE procedures. MATERIAL AND METHODS: In total, 30 patients with 35 HCC nodules treated in the period between January 2019 and November 2021. For each patient, a post-processing software leading to a two-dimensional perfusion angiography was applied on each angiography performed via balloon microcatheter, before and after inflation. On the colour map obtained, reflecting the evolution of contrast intensity change over time, five regions of interests (ROIs) were assessed: one on the tumour (ROI-t), two in the immediate peritumoural healthy liver parenchyma (ROI-ihl) and two in the peripheral healthy liver parenchyma (ROI-phl). The results have been interpreted with a novel in silico model that simulates the hemodynamics of the hepatic arterial system. RESULTS: Among the ROIs drawn inside the same segment of target lesion, the time-to-peak of the ROI-t and of the ROI-ihl have a significantly higher mean value when the balloon was inflated compared with the ROIs obtained with deflated balloon (10.33 ± 3.66 s vs 8.87 ± 2.60 s (p = 0.015) for ROI-t; 10.50 ± 3.65 s vs 9.23 ± 2.70 s (p = 0.047) for ROI-ihl). The in silico model prediction time-to-peak delays when balloon was inflated, match with those observed in vivo. The numerical flow analysis shows how time-to-peak delays are caused by the obstruction of the balloon-occluded artery and the opening of intra-hepatic collateral. CONCLUSION: The measurements identify predictively the flow redistribution in the hepatic arteries during b-TACE, supporting a proper positioning of the balloon microcatheter.

Clinical prediction of microvascular invasion in hepatocellular carcinoma using an MRI-based graph convolutional network model integrated with nomogram.

OBJECTIVES: Based on enhanced MRI, a prediction model of microvascular invasion (MVI) for hepatocellular carcinoma (HCC) was developed using graph convolutional network (GCN) combined nomogram. METHODS: We retrospectively collected 182 HCC patients confirmed histopathologically, all of them performed enhanced MRI before surgery. The patients were randomly divided into training and validation groups. Radiomics features were extracted from the arterial phase (AP), portal venous phase (PVP), and delayed phase (DP), respectively. After removing redundant features, the graph structure by constructing the distance matrix with the feature matrix was built. Screening the superior phases and acquired GCN Score (GS). Finally, combining clinical, radiological and GS established the predicting nomogram. RESULTS: 27.5% (50/182) patients were with MVI positive. In radiological analysis, intratumoural artery (P = 0.007) was an independent predictor of MVI. GCN model with grey-level cooccurrence matrix-grey-level run length matrix features exhibited area under the curves of the training group was 0.532, 0.690, and 0.885 and the validation group was 0.583, 0.580, and 0.854 for AP, PVP, and DP, respectively. DP was selected to develop final model and got GS. Combining GS with diameter, corona enhancement, mosaic architecture, and intratumoural artery constructed a nomogram which showed a C-index of 0.884 (95% CI: 0.829-0.927). CONCLUSIONS: The GCN model based on DP has a high predictive ability. A nomogram combining GS, clinical and radiological characteristics can be a simple and effective guiding tool for selecting HCC treatment options. ADVANCES IN KNOWLEDGE: GCN based on MRI could predict MVI on HCC.

Perfusion of hepatocellular carcinomas measured by diffusion-derived vessel density biomarker: Higher hepatocellular carcinoma perfusion than earlier intravoxel incoherent motion reports.

Diffusion-derived vessel density (DVDD) is a physiological surrogate of the area of microvessels per unit tissue area. DDVD is calculated according to DDVD(b0b2) = Sb0/ROIarea0 - Sb2/ROIarea2, where Sb0 and Sb2 refer to the liver signal when b is 0 or 2 s/mm2. Pathohistological studies and contrast-enhanced CT/MRI data showed higher blood volume in hepatocellular carcinoma (HCC) relative to native liver tissue. With intravoxel incoherent motion (IVIM) imaging, most authors paradoxically reported a decreased perfusion fraction of HCC relative to the adjacent liver. This study applied DDVD to assess the perfusion of HCC. MRI was performed with a 3.0-T magnet. Diffusion-weighted images with b-values of 0 and 2 s/mm2 were acquired in 72 HCC patients. Thirty-two patients had microvascular invasion (MVI(+)) and 40 patients did not have microvascular invasion (MVI(-)). Fifty-eight patients had Edmondson-Steiner grade I or II HCC, and 14 patients had Edmondson-Steiner grade III or IV HCC. DDVD measurement was conducted on the axial slice that showed the largest HCC size. DDVD(b0b2) T/L = HCC DDVD(b0b2)/liver DDVD(b0b2). DDVD(b0b2) T/L median (95% confidence interval) of all HCCs was 2.942 (2.419-3.522), of MVI(-) HCCs was 2.699 (2.030-3.522), of MVI(+) HCCs was 2.988 (2.423-3.990), of Edmondson-Steiner grade I/II HCCs was 2.873 (2.277-3.465), and of Edmondson-Steiner grade III/IV HCCs was 3.403 (2.008-4.485). DDVD(b0b2) T/L approximately agrees with contrast agent dynamically enhanced CT/MRI literature data, whereas it differs from earlier IVIM study results, where HCC perfusion fraction was paradoxically lower relative to native liver tissue. A weak trend was noted with MIV(+) HCCs had a higher DDVD(b0b2) T/L than that of MVI(-) HCCs, and a weak trend was noted with the poorly differentiated group of HCCs (Edmondson-Steiner grade III and IV) had a higher DDVD(b0b2) T/L than that of the better differentiated group of HCCs (Edmondson-Steiner grade I and II).

The Incidences and Related CT Features of Vascular Lake Phenomenon on Angiography Before Chemoembolization.

PURPOSE: To elucidate incidence rates of vascular lake phenomenon (VLP) in hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), hepatic metastasis (HMT) on transarterial angiography before chemoembolization, and to identity CT features predictive for it. MATERIALS AND METHODS: A comprehensive evaluation involved 665 subjects for incidence analysis, comprising 527 of HCC, 33 of ICC and 105 of HMT. VLP was characterized as intratumoral contrast material pool persisting late into venous phase. Incidences were cataloged on both super-selective and common hepatic artery angiography. For CT features analysis, a subset of 182 cases were analyzed. Enhancement ratio served as an index for comparative analysis of nodule enhancement degrees. RESULTS: In HCC, incidence of VLP ascertained via super-selective angiography was 13.5%, whereas it as 7.8% on common hepatic artery angiography. Remarkably, no incidences of VLP were recorded in either ICC or HMT cases. On pre-interventional CT, the prevalence of pseudocapsule was statistically greater in VLP group than Non-VLP group (66.6% vs. 37.6%, P = 0.015). The Houndsfield units (HU) of tumors in plain scan (P = 0.007), arterial phase (P = 0.001), venous phase (P = 0.041), arterial phase enhancement ratio (P < 0.001) were statistically higher in VLP group compared to Non-VLP group. Arterial phase enhancement ratio (P = 0.025), presence of pseudocapsule (P = 0.001), HU of tumor in plain scan (P = 0.035) serve as independent risk factors for VLP manifestation. CONCLUSION: VLP is a distinct angiography phenomenon uniquely associated with HCC. High arterial phase enhancement ratio, presence of pseudocapsule, high HU of tumor in plain scan are independent risk factors for VLP.

Preoperative evaluation of microvascular invasion in hepatocellular carcinoma with a radiological feature-based nomogram: a bi-centre study.

PURPOSE: To develop a nomogram for preoperative assessment of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) based on the radiological features of enhanced CT and to verify two imaging techniques (CT and MRI) in an external centre. METHOD: A total of 346 patients were retrospectively included (training, n = 185, CT images; external testing 1, n = 90, CT images; external testing 2, n = 71, MRI images), including 229 MVI-negative patients and 117 MVI-positive patients. The radiological features and clinical information of enhanced CT images were analysed, and the independent variables associated with MVI in HCC were determined by logistic regression analysis. Then, a nomogram prediction model was constructed. External validation was performed on CT (n = 90) and MRI (n = 71) images from another centre. RESULTS: Among the 23 radiological and clinical features, size, arterial peritumoral enhancement (APE), tumour margin and alpha-fetoprotein (AFP) were independent influencing factors for MVI in HCC. The nomogram integrating these risk factors had a good predictive effect, with AUC, specificity and sensitivity values of 0.834 (95% CI: 0.774-0.895), 75.0% and 83.5%, respectively. The AUC values of external verification based on CT and MRI image data were 0.794 (95% CI: 0.700-0.888) and 0.883 (95% CI: 0.807-0.959), respectively. No statistical difference in AUC values among training set and testing sets was found. CONCLUSION: The proposed nomogram prediction model for MVI in HCC has high accuracy, can be used with different imaging techniques, and has good clinical applicability.

Preoperative Contrast-Enhanced Ultrasound Predicts Microvascular Invasion in Hepatocellular Carcinoma as Accurately as Contrast-Enhanced MR.

OBJECTIVES: Both contrast-enhanced ultrasound (CEUS) and contrast-enhanced magnetic resonance (CEMR) are important imaging methods for hepatocellular carcinoma (HCC). This study aimed to establish a model using preoperative CEUS parameters to predict microvascular invasion (MVI) in HCC, and compare its predictive efficiency with that of CEMR model. METHODS: A total of 93 patients with HCC (39 cases in MVI positive group and 54 cases in MVI negative group) who underwent surgery in our hospital from January 2020 to June 2021 were retrospectively analyzed. Their clinical and imaging data were collected to establish CEUS and CEMR models for predicting MVI. The predictive efficiencies of both models were compared. RESULTS: By the univariate and multivariate regression analyses of patients' clinical information, preoperative CEUS static and dynamic images, we found that serrated edge and time to peak were independent predictors of MVI. The CEUS prediction model achieved a sensitivity of 92.3%, a specificity of 83.3%, and an accuracy of 84.6% (Az: 0.934). By analyzing the clinical and CEMR information, we found that tumor morphology, fast-in and fast-out, peritumoral enhancement, and capsule were independent predictors of MVI. The CEMR prediction model achieved a sensitivity of 97.4%, a specificity of 77.8%, and an accuracy of 83.2% (Az: 0.900). The combination of the two models achieved a sensitivity of 84.6%, a specificity of 87.0%, and an accuracy of 86.2% (Az: 0.884). There was no significant statistical difference in the areas under the ROC curve of the three models. CONCLUSION: The CEUS model and the CEMR model have similar predictive efficiencies for MVI of HCC. CEUS is also an effective method to predict MVI before operation.

Comparison of contrast-enhanced ultrasonography and MRI results obtained by expert and novice radiologists indicating short-term response after transarterial chemoembolisation for hepatocellular carcinoma.

AIM: To evaluate inter-reader agreement between novice and expert radiologists in assessing contrast-enhanced ultrasonography (CEUS) and magnetic resonance imaging (MRI) images for detecting viable tumours with different sizes after conventional transarterial chemoembolisation (cTACE). MATERIALS AND METHODS: This prospective study included patients who had less than five hepatomas and who underwent cTACE. Hepatomas with one or two feeding arteries were selected as target lesions. CEUS and MRI were performed within 1 week after cTACE to evaluate viable tumours. RESULTS: The expert group had higher kappa values in evaluating all tumour sizes via CEUS compared with MRI. The novice group had similar kappa values. In patients with tumours measuring ≤3 cm, the expert group had higher kappa values in reading CEUS compared with MRI images; however, in the novice group, the kappa value was lower in evaluating CEUS compared with MRI images. In patients with tumours measuring >3 cm, the expert and novice groups had good to excellent kappa values. The confidence level of the two groups in reading MRI images was high; however, the novice group had a lower confidence level. CONCLUSION: CEUS is a convenient, cost-effective, and easy to apply imaging tool that can help interventionists perform early detection of viable hepatocellular carcinoma post-TACE. It has a higher inter-rater agreement in interpreting CEUS images compared with MRI images among expert radiologists even when they are extremely familiar with post-cTACE MRI images. In novice radiologists, there may be a learning curve to achieve good consistency in CEUS interpretation.

Clinical and DCE-CT signs in predicting microvascular invasion in cHCC-ICC.

BACKGROUND: To predict the microvascular invasion (MVI) in patients with cHCC-ICC. METHODS: A retrospective analysis was conducted on 119 patients who underwent CT enhancement scanning (from September 2006 to August 2022). They were divided into MVI-positive and MVI-negative groups. RESULTS: The proportion of patients with CEA elevation was higher in the MVI-positive group than in the MVI-negative group, with a statistically significant difference (P = 0.02). The MVI-positive group had a higher rate of peritumoral enhancement in the arterial phase (P = 0.01) whereas the MVI-negative group had more oval and lobulated masses (P = 0.04). According to the multivariate analysis, the increase in CEA (OR = 10.15, 95% CI: 1.11, 92.48, p = 0.04), hepatic capsular withdrawal (OR = 4.55, 95% CI: 1.44, 14.34, p = 0.01) and peritumoral enhancement (OR = 6.34, 95% CI: 2.18, 18.40, p < 0.01) are independent risk factors for predicting MVI. When these three imaging signs are combined, the specificity of MVI prediction was 70.59% (series connection), and the sensitivity was 100% (parallel connection). CONCLUSIONS: Our multivariate analysis found that CEA elevation, liver capsule depression, and arterial phase peritumoral enhancement were independent risk factors for predicting MVI in cHCC-ICC.

Microvascular invasion-negative hepatocellular carcinoma: Prognostic value of qualitative and quantitative Gd-EOB-DTPA MRI analysis.

OBJECTIVES: The purpose of this study was to establish a model for predicting the prognosis of patients with microvascular invasion (MVI)-negative hepatocellular carcinoma (HCC) based on qualitative and quantitative analyses of Gd-EOB-DTPA magnetic resonance imaging (MRI). MATERIALS AND METHODS: Consecutive patients with MVI-negative HCC who underwent preoperative Gd-EOB-DTPA MRI between January 2015 and December 2019 were retrospectively enrolled.In total, 122 patients were randomly assigned to the training and validation groups at a ratio of 7:3. Univariate and multivariate logistic regression analyses were performed to identify significant clinical parameters and MRI features, including quantitative and qualitative parameters associated with prognosis, which were incorporated into a predictive nomogram. The end-point of this study was recurrence-free survival. Outcomes were compared between groups using the Kaplan-Meier method with the log-rank test. RESULTS: During a median follow-up period of 58.86 months, 38 patients (31.15 %) experienced recurrence. Multivariate analysis revealed that lower relative enhancement ratio (RER), hepatobiliary phase hypointensity without arterial phase hyperenhancement, Liver Imaging Reporting and Data System category, mild-moderate T2 hyperintensity, and higher aspartate aminotransferase levels were risk factors associated with prognosis and then incorporated into the prognostic model. C-indices for training and validation groups were 0.732 and 0.692, respectively. The most appropriate cut-off value for RER was 1.197. Patients with RER ≤ 1.197 had significantly higher postoperative recurrence rates than those with RER > 1.197 (p = 0.004). CONCLUSION: The model integrating qualitative and quantitative imaging parameters and clinical parameters satisfactorily predicted the prognosis of patients with MVI-negative HCC.

Application Value of 64-slice Multidetector Spiral CT Contrast-enhanced Scan in Maxillofacial Soft Tissue Hypervascular Tumours.

OBJECTIVE: To evaluate the diagnostic ability and clinical imaging features in maxillofacial soft tissue hypervascular tumours by 64-slice multidetector spiral computed tomography (64-MDCT) contrast-enhanced scanning. METHODS: In a retrospective study of 21 cases of hypervascular tumours, the degree of blood supply and indexes were assessed, and the pathological results were used as the diagnostic gold standard to evaluate the sensitivity and specificity of 64-MDCT plain scan and enhanced CT in the diagnosis of oral and maxillofacial soft tissue hypervascular tumours, using the receiver operating characteristic curve to analyse and evaluate the efficacy. RESULTS: Among 21 patients, the diagnostic accuracy of 64-MDCT contrast-enhanced scan was 90.48%, the area under the curve of venous phase CT value was 0.80, the sensitivity was 83.30% and the specificity was 72.73%. CONCLUSION: 64-MDCT contrast-enhanced scan can be used to evaluate the blood supply of maxillofacial soft tissue hypervascular tumours before an operation. The CT value in the venous phase of tumours has the highest diagnostic effectiveness, which can reduce the risk of blood loss during surgery for maxillofacial hypervascular tumours. In addition, it has certain guiding significance for the formulation of clinical treatment plans.

Perfusion parameters of triphasic computed tomography hold preoperative prediction value for microvascular invasion in hepatocellular carcinoma.

The purpose of this study was to evaluate perfusion parameters of triphasic computed tomography (CT) scans in predicting microvascular invasion (MVI) in hepatocellular carcinoma (HCC). All patients were pathologically diagnosed as HCC and underwent triple-phase enhanced CT imaging, which was used to calculate the blood perfusion parameters of hepatic arterial supply perfusion (HAP), portal vein blood supply perfusion (PVP), hepatic artery perfusion Index (HPI), and arterial enhancement fraction (AEF). Receiver operating characteristic (ROC) curve was used to evaluate the performance. The mean values of PVP(Min), AEF(Min), the difference in PVP, HPI and AEF related parameters, the relative PVP(Min) and AEF(Min) in MVI negative group were significantly higher than those in MVI positive group, while for the difference in HPI(Max), the relative HPI(Max) and AEF(Max), the value of MVI positive group significantly higher than that of negative group. The combination of PVP, HPI and AEF had the highest diagnostic efficacy. The two parameters related to HPI had the highest sensitivity, while the combination of PVP related parameters had higher specificity. A combination of perfusion parameters in patients with HCC derived from traditional triphasic CT scans can be used as a preoperative biomarker for predicting MVI.

Prediction of microvascular invasion in combined hepatocellular-cholangiocarcinoma based on preoperative contrast-enhanced CT and clinical data.

OBJECTIVE: Microvascular invasion (MVI) is significantly associated with prognosis in combined hepatocellular-cholangiocarcinoma (cHCC-CCA) patients. The study aimed to explore the value of preoperative contrast-enhanced CT (CECT) features and clinical data in predicting MVI of cHCC-CCA. METHODS: A total of 33 patients with MVI-positive and 27 with MVI-negative were enrolled, and underwent preoperative CECT imaging from January 2016 to December 2021. Preoperative clinical data and CECT imaging features were retrospectively analyzed. Univariable and multivariable logistic regression analysis were performed to identify potential predictors of MVI in cHCC-CCA. The diagnostic performance was evaluated by the receiver operating characteristic (ROC) curve and its area under the curve (AUC) value. RESULTS: The mean age of the patients was 54.0 ±â€¯10.3 years, and 53 of the 60 patients (88.3%) were male. Preoperative imaging features on CECT (non-smooth contour and arterial phase peritumoral enhancement) and clinical data (hepatitis B virus (HBV) infection and protein induced by vitamin K absence or antagonist-II (PIVKA-II)) were highly distinct between those in MVI-positive group and MVI-negative group. On multivariable logistic analysis, arterial phase peritumoral enhancement (odds ratio (OR), 6.514; 95% confidence interval (CI), 1.588-26.728, p = 0.012) and high serum PIVKA-II level (OR, 6.810; 95% CI, 1.796-25.820, p = 0.005) were independent predictors associated with MVI of cHCC-CCA. The combination of these two predictors had high sensitivity (31/33, 93.9%; 95% CI, 80.4% - 98.3%) in the prediction of MVI with an area under the receiver operating characteristic (ROC) curve of 0.763 (95% CI, 0.635-0.863). CONCLUSIONS: The findings indicated that arterial phase peritumoral enhancement on preoperative CECT and high serum PIVKA-II level were identified as potential predictors for MVI in cHCC-CCA patients.

Short-term changes of angiogenesis factors after transarterial radioembolization in hepatocellular carcinoma patients.

PURPOSE: To analyze changes in angiogenesis factors after transarterial radioembolization (TARE) with Yttrium- 90-loaded resin microspheres in hepatocellular carcinoma (HCC) patients. METHODS: Interleukin-6, interleukin-8, hepatocyte growth factor, platelet-derived growth factor, fibroblast growth factor, vascular endothelial growth factor-A (VEGF-A), and angiopoietin-2 levels in 26 patients were measured before TARE and on day 1, 7, 14, and 30 after TARE and evaluated regarding radiological response. RESULTS: In the sixth month of follow-up, 11 (42.30%) patients had a complete or partial response to treatment, while progressive disease was found in 15 (57.69%) patients. The percentage changes in VEGF-A in the non-responders on day 30 (P = 0.034) after TARE were significantly more obvious. Peak formation rates of VEGF-A were higher in non-responders (P = 0.036). CONCLUSION: Short-term changes in angiogenesis factors in HCC patients after TARE with Yttrium-90-loaded resin microspheres fluctuate with different amplitudes at different times. The upregulation of growth factors has a prognostic capacity. Changes in VEGF-A after TARE may be helpful for the early recognition of non-responders.

Comparison of preoperative ultrasound and MRI in the diagnosis of microvascular invasion in hepatocellular carcinoma.

Ultrasound has few reports on its application in prediction of microvascular invasion (MVI) in hepatocellular carcinoma (HCC). The purpose of this study was to explore the diagnostic efficacies of preoperative ultrasound and magnetic resonance imaging (MRI) for HCC MVI and compare these two imaging methods for the diagnosis of this condition. The clinical and preoperative ultrasound and MR imaging data of 26 patients with newly diagnosed HCC were collected between October 2020 and October 2021. According to the gold standard (postoperative pathology), the patients were divided into MVI-positive and MVI-negative groups, and the efficacies of ultrasound and MRI in diagnosing HCC MVI and the consistency between the two imaging modalities were analyzed. For the preoperative diagnosis of MVI using ultrasound, the sensitivity was 93.33%, the specificity was 81.82%, and the accuracy was 88.46%. For preoperative MRI, the sensitivity was 66.67%, the specificity was 100%, and the accuracy was 80.77%. In diagnosing MVI, the two methods had significantly different efficacy (P = 0.031). Ultrasound and MRI have high diagnostic efficiency for MVI, but the accuracy of preoperative MRI was lower than that of preoperative ultrasound. These results indicate that ultrasound has a certain guiding significance in the diagnosis of HCC MVI.

Dahuang Zhechong pill attenuates hepatic sinusoidal capillarization in liver cirrhosis and hepatocellular carcinoma rat model via the MK/integrin signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Dahuang Zhechong pill (DHZCP), a traditional Chinese medicine, was derived from the famous book Unk "Synopsis of Prescriptions of the Golden Chamber" during the Han dynasty. Owing to its ability to invigorate the circulation of blood in Chinese medicine, DHZCP is usually used for treating liver cirrhosis (LC) and hepatocellular carcinoma (HCC). Clinical application have shown that DHZCP exhibits satisfactory therapeutic effects in HCC adjuvant therapy; however, little is known about its underlying mechanisms. AIM OF THE STUDY: We aimed to clarify the mechanism of DHZCP against hepatic sinusoidal capillarization in rats with LC and HCC by inhibiting the MK/integrin signaling pathway of liver sinusoidal endothelial cells (LSECs). MATERIALS AND METHODS: The contents of 29 characteristic components in DHZCP were determined by ultraperformance liquid chromatography-tandem mass spectrometry. DEN (Diethylnitrosamine)-induced LC and HCC rat models were constructed, and DHZCP was administered when the disease entered the LC stage. After 4 or 12 weeks of administration, hematoxylin and eosin staining, Masson staining, Metavir score, and SSCP (Single strand conformation polymorphism) gene mutation detection were used to confirm tissue fibrosis and cancer. The levels of NO, ET-1 and TXA2, which can regulate vasomotor functions and activate the MK/Itgα6/Src signaling pathway were evaluated by using immunohistochemistry, chemiluminescence, immunofluorescence, Western blot analysis, and enzyme-linked immunosorbent assay (ELISA). Similar methods were also used to evaluate the levels of VEGF, VEGFR, Ang-2 and Tie, which can promote pathological angiogenesis and activate the MK/Itgα4/NF-κB signaling pathway. In vitro cell experiments were performed using potential pharmacodynamic molecules targeting integrins in DHZCP were selected by molecular docking, and the effects of these molecules on the function of LSECs were studied by Itgα4+ and Itgα6+ cell models. RESULTS: At the stage of LC, the animal experiments demonstrated that DHZCP mainly inhibited the MK/Itgα6 signaling pathway to increase the number and size of hepatic sinus fenestration, reversed the ET-1/NO and TXA2/NO ratios, regulated hepatic sinus relaxation and contraction balance, reduced the portal vein pressure, and inhibited cirrhotic carcinogenesis. At the HCC stage, DHZCP could also significantly inhibit the MK/Itgα4 signaling pathway, reduce pathological angiogenesis, and alleviate disease progression. The results of the cell experiments showed that Rhein, Naringenin, Liquiritin and Emodin-8-O-ß-D-glucoside (PMEG) were involved in vascular regulation by affecting the MK/integrin signaling pathway. Liquiritin and PMEG mainly blocked the MK/α6 signal, which is important in regulating the vasomotor function of the liver sinus. Naringenin and Rhein mainly acted by blocked the signaling of MK/α4 action signal, which are potent molecules that inhibit pathological angiogenesis. CONCLUSIONS: DHZCP could improve the hepatic sinusoidal capillarization of LC and HCC by inhibiting the MK/Itgα signaling pathway and inhibited disease progression. Rhein, Naringenin, Liquiritin and PMEG were the main active molecules that affected the MK/Itgα signaling pathway.