Non-invasive prediction model of axillary lymph node status in patients with early-stage breast cancer: a feasibility study based on dynamic contrast-enhanced-MRI radiomics.

OBJECTIVES: Accurate axillary evaluation plays an important role in prognosis and treatment planning for breast cancer. This study aimed to develop and validate a dynamic contrast-enhanced (DCE)-MRI-based radiomics model for preoperative evaluation of axillary lymph node (ALN) status in early-stage breast cancer. METHODS: A total of 410 patients with pathologically confirmed early-stage invasive breast cancer (training cohort, N = 286; validation cohort, N = 124) from June 2018 to August 2022 were retrospectively recruited. Radiomics features were derived from the second phase of DCE-MRI images for each patient. ALN status-related features were obtained, and a radiomics signature was constructed using SelectKBest and least absolute shrinkage and selection operator regression. Logistic regression was applied to build a combined model and corresponding nomogram incorporating the radiomics score (Rad-score) with clinical predictors. The predictive performance of the nomogram was evaluated using receiver operator characteristic (ROC) curve analysis and calibration curves. RESULTS: Fourteen radiomic features were selected to construct the radiomics signature. The Rad-score, MRI-reported ALN status, BI-RADS category, and tumour size were independent predictors of ALN status and were incorporated into the combined model. The nomogram showed good calibration and favourable performance for discriminating metastatic ALNs (N + (≥1)) from non-metastatic ALNs (N0) and metastatic ALNs with heavy burden (N + (≥3)) from low burden (N + (1-2)), with the area under the ROC curve values of 0.877 and 0.879 in the training cohort and 0.859 and 0.881 in the validation cohort, respectively. CONCLUSIONS: The DCE-MRI-based radiomics nomogram could serve as a potential non-invasive technique for accurate preoperative evaluation of ALN burden, thereby assisting physicians in the personalized axillary treatment for early-stage breast cancer patients. ADVANCES IN KNOWLEDGE: This study developed a potential surrogate of preoperative accurate evaluation of ALN status, which is non-invasive and easy-to-use.

The use of SNAP and T1-weighted VISTA in cervical artery dissection.

BACKGROUND AND PURPOSE: Some cervical artery dissection (CAD) can't be easily confirmed by commonly used angiography techniques in clinical practice. We aimed to compare the abilities of the vessel wall magnetic resonance imaging (MRI) techniques including simultaneous noncontrast angiography and intraplaque hemorrhage (SNAP) sequence and T1-weighted volumetric isotropic turbo spin echo acquisition (T1-w VISTA) sequence alone for evaluating CAD. MATERIALS AND METHODS: From July 2017 to October 2020, 59 patients underwent MRI examinations including SNAP and T1-w VISTA sequences for cervical artery pathologies. SNAP and T1-w VISTA images were retrospectively and independently reviewed to evaluate their diagnostic performances of CAD by using the final diagnosis as the reference standard which was established by clinical history, physical examination, and all available images. The agreement between T1-w VISTA and SNAP in the identification of the imaging features of CAD, including intramural hematoma (IMH), intimal flap, and double lumen, were compared. The IMH-wall contrasts by T1-w VISTA and SNAP were also compared. RESULTS: CAD was confirmed in 43 of the 59 patients. T1-w VISTA and SNAP showed the same diagnostic performance, and their consistencies with the final diagnosis were good (κ = 0.776, p < 0.001). The sensitivity and specificity in CAD diagnosis were 0.978 and 0.750 for T1-w VISTA and SNAP. The IMH, intimal flap, and double lumen observed on SNAP were also determined by T1-w VISTA (κ = 1.000, p < 0.001 for all). The SNAP sequence showed higher IMH-wall contrast than T1-w VISTA (7.34 ± 4.56 vs. 3.12 ± 1.17, p < 0.001). CONCLUSIONS: SNAP and T1-w VISTA sequences had the same performance in CAD diagnosis, thus they were both recommended. In addition, SNAP showed better IMH-wall contrast than T1-w VISTA.

Intraplacental T2-hypointense bands may help predict placental invasion depth and postpartum hemorrhage in placenta accrete spectrum disorders in high-risk gravid patients.

INTRODUCTION: Accurate noninvasive prenatal diagnosis of placenta accreta spectrum (PAS) disorder is critical for delivery management. PURPOSE: To evaluate the diagnostic ability of MRI features in predicting the PAS, invasive depth and postpartum hemorrhage (PPH) in high-risk gravid patients. MATERIALS AND METHODS: Between February 2019 and November 2020, women with ultrasound (US)-suspected PAS were enrolled. With the exclusion criteria, 80 women were included in the study. Two experienced genitourinary radiologists reviewed and recorded the MRI features. The chi square test was used to compare the effectiveness of MRI features. Relative risk ratios were computed to test the association of intraplacental T2-hypointense bands with poor outcomes of cesarean section. Receiver operating characteristic (ROC) analyses based on the number and area of intraplacental T2-hypointense bands were used to predict PAS, invasion depth, and PPH. RESULTS: PAS was diagnosed in 56 of 80 women (70%). At delivery, 24 of 80 women (30%) experienced PPH (≥1000 mL). Intraplacental T2-hypointense bands were detected at MRI in 28 of 56 women with PAS (50%). The relative risk ratio of intraplacental T2-hypointense bands was 1.51 for PAS, 3.17 for depth of PAS invasiveness and 4.74 for PPH. The largest areas of intraplacental T2-hypointense bands for predicting PAS, invasion depth and PPH were 0.66 cm2, 1.68 cm2 and 1.99 cm2, respectively. DISCUSSION: The appearance of intraplacental T2-hypointense bands has important diagnostic value for PAS, its invasion depth and PPH. The area of the largest T2-hypointense band in the placenta can predict poor outcomes of cesarean section.

A Radiomics Signature-Based Nomogram to Predict the Progression-Free Survival of Patients With Hepatocellular Carcinoma After Transcatheter Arterial Chemoembolization Plus Radiofrequency Ablation.

Objective: The study aims to establish an magnetic resonance imaging radiomics signature-based nomogram for predicting the progression-free survival of intermediate and advanced hepatocellular carcinoma (HCC) patients treated with transcatheter arterial chemoembolization (TACE) plus radiofrequency ablation Materials and Methods: A total of 113 intermediate and advanced HCC patients treated with TACE and RFA were eligible for this study. Patients were classified into a training cohort (n = 78 cases) and a validation cohort (n = 35 cases). Radiomics features were extracted from contrast-enhanced T1W images by analysis kit software. Dimension reduction was conducted to select optimal features using the least absolute shrinkage and selection operator (LASSO). A rad-score was calculated and used to classify the patients into high-risk and low-risk groups and further integrated into multivariate Cox analysis. Two prediction models based on radiomics signature combined with or without clinical factors and a clinical model based on clinical factors were developed. A nomogram comcined radiomics signature and clinical factors were established and the concordance index (C-index) was used for measuring discrimination ability of the model, calibration curve was used for measuring calibration ability, and decision curve and clinical impact curve are used for measuring clinical utility. Results: Eight radiomics features were selected by LASSO, and the cut-off of the Rad-score was 1.62. The C-index of the radiomics signature for PFS was 0.646 (95%: 0.582-0.71) in the training cohort and 0.669 (95% CI:0.572-0.766) in validation cohort. The median PFS of the low-risk group [30.4 (95% CI: 19.41-41.38)] months was higher than that of the high-risk group [8.1 (95% CI: 4.41-11.79)] months in the training cohort (log rank test, z = 16.58, p < 0.001) and was verified in the validation cohort. Multivariate Cox analysis showed that BCLC stage [hazard ratio (HR): 2.52, 95% CI: 1.42-4.47, p = 0.002], AFP level (HR: 2.01, 95% CI: 1.01-3.99 p = 0.046), time interval (HR: 0.48, 95% CI: 0.26-0.87, p = 0.016) and radiomics signature (HR 2.98, 95% CI: 1.60-5.51, p = 0.001) were independent prognostic factors of PFS in the training cohort. The C-index of the combined model in the training cohort was higher than that of clinical model for PFS prediction [0.722 (95% CI: 0.657-0.786) vs. 0.669 (95% CI: 0.657-0.786), p＜0.001]. Similarly, The C-index of the combined model in the validation cohort, was higher than that of clinical model [0.821 (95% CI: 0.726-0.915) vs. 0.76 (95% CI: 0.667-0.851), p = 0.004]. The calibration curve, decision curve and clinical impact curve showed that the nomogram can be used to accurately predict the PFS of patients. Conclusion: The radiomics signature was a prognostic risk factor, and a nomogram combined radiomics and clinical factors acts as a new strategy for predicted the PFS of intermediate and advanced HCC treated with TACE plus RFA.

Correction to: Integrated analysis reveals critical glycolytic regulators in hepatocellular carcinoma.

An amendment to this paper has been published and can be accessed via the original article.

Triptonide Modulates MAPK Signaling Pathways and Exerts Anticancer Effects via ER Stress-Mediated Apoptosis Induction in Human Osteosarcoma Cells.

BACKGROUND: Osteosarcoma (OS) is the most common primary malignancy arise from bone and is one of the causes of cancer-related deaths. Triptonide (TN), a diterpenoid epoxide presented in Tripterygium wilfordii, is shown to possess a broad spectrum of biological properties. METHODS: In this study, we investigate the growth inhibitory effect of TN against human OS cells and its underlying molecular mechanism of action. RESULTS: Findings of our in vitro study revealed that TN exhibited a dose-dependent cytotoxic effect in MG63 and U-2OS cells. ROS-mediated cytotoxic effect was achieved in OS cells treated with TN which was reversed upon NAC treatment. Significantly, increased expression of PERK, p-EIF2, GRP78, ATF4 and CHOP in TN-treated OS cells unfolds the molecular mechanism of TN targets ER stress-mediated apoptosis. Modulation of ERK MAPK pathway was also observed as evidenced by the increased phosphorylation of ERK (p-ERK) and p-p38 in TN-treated OS cells. CONCLUSION: Altogether, the outcome of the study for the first time revealed that TN exhibited its potential chemotherapeutic effects through ROS-mediated ER stress-induced apoptosis via p38 and ERK MAPK signaling pathways.

ZFP36 Binds With PRC1 to Inhibit Tumor Growth and Increase 5-Fu Chemosensitivity of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the fifth common cause of tumor-related death worldwide. ZFP36, a RNA-binding protein, decreases in many cancers and its role in HCC remains unclear. This study aimed to investigate the underlying mechanisms by which ZFP36 inhibited HCC progression and increased fluorouracil (5-Fu) sensitivity. We found that ZFP36 was downregulated and PRC1 was upregulated in HCC tissues compared with adjacent non-tumor tissues. In vitro investigation presented that ZFP36 acted as a tumor suppressor, while overexpression of PRC1 increased cell proliferation, colony formation and invasion. Further investigations demonstrated that overexpression of ZFP36 inhibited tumor growth and promoted 5-Fu sensitivity in xenograft tumor mice model, which could be reversed when PRC1 overexpressed simultaneously. Luciferase reporter assays and Ribonucleoprotein immunoprecipitation analysis indicated that ZFP36 could bind to adenylate uridylate-rich elements located in PRC1 mRNA 3'UTR to downregulate PRC1 expression. Taken together, our findings identified that ZFP36 regulated PRC1 to exert anti-tumor effect, which suggested a potential therapeutic strategy for treating HCC by exploiting ZFP36/PRC1 axis.

Integrated analysis reveals critical glycolytic regulators in hepatocellular carcinoma.

BACKGROUND: Cancer cells primarily utilize aerobic glycolysis for energy production, a phenomenon known as the Warburg effect. Increased aerobic glycolysis supports cancer cell survival and rapid proliferation and predicts a poor prognosis in cancer patients. METHODS: Molecular profiles from The Cancer Genome Atlas (TCGA) cohort were used to analyze the prognostic value of glycolysis gene signature in human cancers. Gain- and loss-of-function studies were performed to key drivers implicated in hepatocellular carcinoma (HCC) glycolysis. The molecular mechanisms underlying Osteopontin (OPN)-mediated glycolysis were investigated by real-time qPCR, western blotting, immunohistochemistry, luciferase reporter assay, and xenograft and diethyl-nitrosamine (DEN)-induced HCC mouse models. RESULTS: Increased glycolysis predicts adverse clinical outcome in many types of human cancers, especially HCC. Then, we identified a handful of differentially expressed genes related to HCC glycolysis. Gain- and loss-of-function studies showed that OPN promotes, while SPP2, LECT2, SLC10A1, CYP3A4, HSD17B13, and IYD inhibit HCC cell glycolysis as revealed by glucose utilization, lactate production, and extracellular acidification ratio. These glycolysis-related genes exhibited significant tumor-promoting or tumor suppressive effect on HCC cells and these effects were glycolysis-dependent. Mechanistically, OPN enhanced HCC glycolysis by activating the αvß3-NF-κB signaling. Genetic or pharmacological blockade of OPN-αvß3 axis suppressed HCC glycolysis in xenograft tumor model and hepatocarcinogenesis induced by DEN. CONCLUSIONS: Our findings reveal crucial determinants for controlling the Warburg metabolism in HCC cells and provide a new insight into the oncogenic roles of OPN in HCC. Video Abstract.

Efficacy and Safety of TACE Combined With Sorafenib Plus Immune Checkpoint Inhibitors for the Treatment of Intermediate and Advanced TACE-Refractory Hepatocellular Carcinoma: A Retrospective Study.

Purpose: The study aims to retrospectively investigate the efficacy and safety of sorafenib combined with transarterial chemoembolization (TACE) (TACE+Sor) vs. TACE combined with sorafenib plus immune checkpoint inhibitors (TACE+Sor+ICIs) in treating intermediate and advanced TACE-refractory hepatocellular carcinoma (HCC). Materials and Methods: This study was approved by the ethics committee of Lisui Hospital, Zhejiang University, China. From January 2016 to June 2020, 51 eligible patients with intermediate or advanced TACE-refractory HCC received TACE+Sor (n = 29) or TACE+Sor+ICIs (n = 22). The differences in tumor response, adverse events (AEs), progression-free survival (PFS), and overall survival (OS) were compared between the two groups. Factors affecting PFS and OS were determined by Cox regression. Results: The disease control rate was higher in the TACE+Sor+ICIs group than in the TACE+Sor group (81.82 vs. 55.17%, P = 0.046). Compared with the TACE+Sor group, PFS and OS were prolonged in the TACE+Sor+ICIs group (median PFS: 16.26 vs. 7.30 months, P < 0.001; median OS: 23.3 vs. 13.8 months, P = 0.012). Multivariate analysis showed that BCLC stage, alpha-fetoprotein and treatment were independent factors of PFS; BCLC, Child-Pugh class, ablation after disease progression and treatment were independent predictive factors of OS. Four patients in the TACE+Sor+ICIs group and three patients in the TACE+Sor group suffered from dose reduction or interruption (18.18 vs. 10.34%, P = 0.421). The incidence of ICI-related AEs in the TACE+Sor+ICIs group was well-controlled. Conclusion: The therapeutic schedule of TACE+Sor+ICIs demonstrated efficacy and safety in intermediate and advanced TACE-refractory HCC.

Value of TSCT Features for Differentiating Preinvasive and Minimally Invasive Adenocarcinoma From Invasive Adenocarcinoma Presenting as Subsolid Nodules Smaller Than 3 cm.

BACKGROUND: To distinguish preinvasive (adenocarcinoma in situ/atypical adenomatous hyperplasia) and minimally invasive adenocarcinoma (MIA) from invasive adenocarcinoma (IA) appearing as solitary subsolid nodules (SSNs) less than 3 cm based on thin-section computed tomography (TSCT) features to guide therapeutic approaches. METHODS: A total of 154 lesions that were histopathologically confirmed to have pre/minimally invasive adenocarcinoma (hereafter pre/MIA) and IA presenting as part-solid nodules (PSNs) or pure ground-glass nodules (pGGNs) were retrospectively reviewed. The TSCT features, including diameter, area, CT value, shape, air bronchogram, margins, and location, were compared and assessed. Receiver operating characteristic analyses were conducted to determine the cut-off values for the qualitative variables and their diagnostic performances. RESULTS: Of 154 nodules, 89 IA, 53 MIA, eight adenocarcinoma in situ, and four atypical adenomatous hyperplasia lesions were found. Univariate and multivariate logistic regression of the pre/MIA and IA lesions were compared and analyzed among PSNs and pGGNs. Among pGGNs, a significant difference was found in the area (p = 0.004, odds ratio [OR] = 0.124, 95% confidence interval [CI] = 0.300-0.515) between the pre/MIA and IA groups. In PSNs, significant differences were found in the diameter (p = 0.001, OR = 0.171, 95% CI = 0.063-0.467) and CT value (p = 0.001, OR = 0.996, 95% CI = 0.993-0.998) between the pre/MIA and IA groups. According to the corresponding receiver operating characteristic curves, the optimal cut-off tumor area in pGGNs to differentiate pre/MIA from IA was 0.595 cm2. A higher CT value of the lesion (≥ -298.500 HU) and a larger diameter (≥1.450 cm) in PSNs were significantly associated with IA. CONCLUSION: Imaging features from TSCT contribute to distinguishing pre/MIA from IA in solitary subsolid nodules and may contribute to guide the clinical management of these lesions.

Changes in hepatic metabolic profile during the evolution of STZ-induced diabetic rats via an 1H NMR-based metabonomic investigation.

Background: The present study aimed to explore the changes in the hepatic metabolic profile during the evolution of diabetes mellitus (DM) and verify the key metabolic pathways. Methods: Liver samples were collected from diabetic rats induced by streptozotocin (STZ) and rats in the control group at 1, 5, and 9 weeks after STZ administration. Proton nuclear magnetic resonance spectroscopy (1H NMR)-based metabolomics was used to examine the metabolic changes during the evolution of DM, and partial least squares-discriminate analysis (PLS-DA) was performed to identify the key metabolites. Results: We identified 40 metabolites in the 1H NMR spectra, and 11 metabolites were further selected by PLS-DA model. The levels of α-glucose and ß-glucose, which are two energy-related metabolites, gradually increased over time in the DM rats, and were significantly greater than those of the control rats at the three-time points. The levels of choline, betaine, and methionine decreased in the DM livers, indicating that the protective function in response to liver injury may be undermined by hyperglycemia. The levels of the other amino acids (leucine, alanine, glycine, tyrosine, and phenylalanine) were significantly less than those of the control group during DM development. Conclusions: Our results suggested that the hepatic metabolic pathways of glucose, choline-betaine-methionine, and amino acids were disturbed during the evolution of diabetes, and that choline-betaine-methionine metabolism may play a key role.

CPEB1 mediates hepatocellular carcinoma cancer stemness and chemoresistance.

Cancer stem cells (CSCs) are a subpopulation of cells within tumors that are believed to possess pluripotent properties and thought to be responsible for tumor initiation, progression, relapse and metastasis. Cytoplasmic polyadenylation element-binding protein 1 (CPEB1), a sequence-specific RNA-binding protein that regulates mRNA polyadenylation and translation, has been linked to cancer progression and metastasis. However, the involvement of CPEB1 in hepatocellular carcinoma (HCC) remains unclear. In this study, we have demonstrated that CPEB1 directly regulates sirtuin 1 (SIRT1) mRNA to mediate cancer stemness in HCC. Cancer stemness was analyzed by self-renewal ability, chemoresistance, metastasis, expression of stemness-related genes and CSC marker-positive cell populations. The results indicate that CPEB1 is downregulated in HCC. Overexpression of CPEB1 dramatically reduced HCC cell stemness, whereas silencing CPEB1 enhances it. Using site-directed mutagenesis, a luciferase reporter assay, and immunoprecipitation, we found that CPEB1 could directly target the 3'-UTR of SIRT1, control poly(A) tail length and suppress its translation to mediate cancer stemness in vitro and in vivo. Overall, our findings suggest that the negative regulation between CPEB1 and SIRT1 contributes to the suppression of cancer stemness in HCC. CPEB1 may have potential as a therapeutic target in HCC.

miR-590-5p suppresses hepatocellular carcinoma chemoresistance by targeting YAP1 expression.

BACKGROUND: Resistance to chemotherapeutic treatment is a common phenomenon in cancers, especially in hepatocellular carcinoma (HCC). The Hippo signaling pathway has been demonstrated to play a role in tumor initiation, development, and progression. However, little is known about its roles in the HCC chemoresistance. METHODS: In this study, real-time PCR and western blotting were used to identify the expression profile of key components of Hippo signaling pathway between chemoresistant and chemosensitive HCC cell lines. In vitro and in vivo loss- and gain-of-function studies were performed to reveal the effects and related mechanism of microRNA-590-5p/YAP1 axis in the chemoresistant phenotype of HCC cells. FINDINGS: We identified yes-associated protein 1 (YAP1) as the major dysregulated molecules in adriamycin (ADR)-resistant HCC cells. YAP1 was profoundly implicated in the chemoresistant phenotype of HCC cells. Furthermore, microRNA-590-5p was revealed as a functional modulator of YAP1. Importantly, YAP1-mediated chemoresistant phenotype was closely related to increased expression of stemness markers and ATP-binding cassette transporters. HCC patients with poor response to transarterial chemoembolization (TACE) treatment had higher protein level of YAP1 than that in the responsive patients. INTERPRETATION: The microRNA-590-5p/YAP axis plays an important role in the chemotherapeutic resistance of HCC cells, suggesting new adjuvant chemotherapeutic directions in HCC. FUND: National Natural Science Foundation of China, Zhejiang Province Medical and Health Care Key Project, Experimental Animal Science and Technology Projects of Zhejiang Province, Public Welfare Technology Application Research Project of Lishui, Chinese Medicine Science and Technology Projects of Zhejiang Province.

FGFR4 Links Glucose Metabolism and Chemotherapy Resistance in Breast Cancer.

BACKGROUND/AIMS: Poor response to chemotherapy leads to the relapse and metastatic progression of tumors. Reprogrammed glucose metabolism is one of the important hallmarks of cancer that facilitates cancer cell survival, proliferation and chemoresistance. However, the precise fate of glucose metabolism and its role in therapy responsiveness in cancers remains largely unexplored. METHODS: The glycolytic phenotype of doxorubicin (ADR)-resistant breast cancer cells and their parental cells was assessed by measuring glucose uptake, lactate release, and extracellular acidification rate (ECAR). Protein expression was detected by Western blotting analysis and mRNA expression was detected using q-PCR. Cell survival ratio was determined by the cell counting kit 8 assay. The role of fibroblast growth factor receptor 4 (FGFR4) in glycolysis, chemoresistance, and the underlying mechanisms were studied by using gene expression microarray and short hairpin RNA-mediated gene knockdown. RESULTS: We found that glycolytic flux are increased in two doxorubicin (ADR)-resistant breast cancer cell lines compared with their parental wild type cells, as demonstrated by increased glucose uptake, lactate release, and extracellular acidification rate (ECAR). By gene expression microarray, we identified FGFR4 as a critical modulator of ADR resistance and enhanced glucose metabolism. Genetic silencing of FGFR4 increased the chemosensitivity and suppressed the enhanced glycolytic flux in ADR-resistant cells. Mechanistically, activation of FGFR4 signaling in ADR-resistant cells led to the phosphorylation of FGF receptor substrate 2 (FRS2) and further activated the downstream MAPK/ERK signaling. Pharmacological inhibition of FGFR4-FRS2-ERK signaling pathway significantly blocked the chemoresistant and glycolytic phenotypes of ADR-resistant cells. CONCLUSION: Our findings suggest that high levels of FGFR4 can increase glucose metabolism and lead to chemoresistance in breast cancer and reveal the mechanistic basis for targeting FGFR4 as a therapeutic opportunity for chemoresistant tumors.

Effectiveness of the Conservative Therapy for Symptomatic Isolated Celiac Artery Dissection.

OBJECTIVE: To investigate the effectiveness of the conservative therapy for symptomatic isolated celiac artery dissection (ICAD). METHODS: Patients with symptomatic ICAD diagnosed on CT between February 2006 and June 2016 at three institutions were included. RESULTS: During the study period, a total of 24 patients (22 men, 2 women) were included in this retrospective study. Patients most commonly presented with epigastric pain (n = 21) or back pain (n = 3). Initial CT findings included celiac arterial calcification (n = 3); compression of the true lumen (n = 24), including stenosis of the true lumen <50% (n = 14) or ≥50% (n = 10); completely thrombosed (n = 11) or partially thrombosed (n = 5) false lumen; no thrombosis of the false lumen but presence of dissecting aneurysm (n = 8); and dissection extending to the common hepatic (n = 1) or splenic (n = 6) artery. Twenty-three patients recovered after conservative treatment, and one patient who failed conservative treatment recovered after surgical therapy. Of the 23 patients who received conservative treatment, complete or partial remodeling of ICAD was achieved in 18 (78.3%) and 5 (21.7%) patients during 22.1 ± 13.3 months of follow-up. CONCLUSIONS: Conservative treatment can be applied successfully in most patients with symptomatic ICAD. Most cases of symptomatic ICAD resolve spontaneously within 2 years.

High expression of angiogenic factor AGGF1 is an independent prognostic factor for hepatocellular carcinoma.

BACKGROUND: Angiogenesis plays a critical role in tumor growth and metastasis. Angiogenic factor with G patch and FHA domains 1 (AGGF1) has been recently identified as a novel initiator of angiogenesis. However, the function and the prognostic values of AGGF1 in hepatocellular carcinoma remain poorly understood. Our aim is to provide more information to assist design the angiogenesis therapy that targets AGGF1 in HCC. RESULTS: AGGF1-positive frequency in HCC tissues was significantly higher than in peritumor tissues. The high expression of AGGF1 expression in HCC tissue was well associated with the increased expression of VEGF and the high microvessel density (MVD). AGGF1 expression predicts a poor prognosis and AGGF1 was an independent prognostic factor for DFS. METHODS: The expression levels of AGGF1, vascular endothelial growth factor (VEGF) and microvessel density (MVD) were identified by immunohistochemistry in 79 HCC tumor tissues and 24 corresponding peritumor tissues. The expression level of AGGF1 and MVD were quantified by counting the positively stained endothelial cells in the HCC and the peritumor tissue on the immunohistochemically stained tissue slides. The prognostic value of AGGF1 was evaluated by survival analysis. CONCLUSIONS: Our study shows that AGGF1 is identified as the independent prognostic factor for the disease-free survival (DFS) of patients after the surgical resection. contribute to tumor angiogenesis in HCC, which indicates that AGGF1 may be a new potential therapeutic target for anti-angiogenesis treatment for patients with HCC.