Bronchial arterial chemoembolization with Drug-Eluting beads plus sequential chemotherapy for the treatment of stage III and IV lung squamous cell carcinoma.

PURPOSE: This retrospective study aimed to investigate the effectiveness and safety of bronchial arterial chemoembolization with drug-eluting beads (DEB-BACE) plus chemotherapy versus chemotherapy alone in patients with stage III and IV lung squamous cell carcinoma (LSCC) who are not appropriate candidates for radiochemotherapy. MATERIALS AND METHODS: In this retrospective analysis, we screened all adult patients undergoing either DEB-BACE plus chemotherapy or chemotherapy alone for stage III or IV LCSS at authors' center from January 2018 to August 2021. Each 21-day chemotherapy cycle consisted of intravenous injection of gemcitabine (1.0 g/m2) on days 1 and 8 and cisplatin 75 (mg/m2) on day 1. The planned cycles were 4. DEB-BACE consisted of microcatheter infusion of CalliSpheres beads carrying cisplatin (75 mg/m2) and gemcitabine (1.0 g/m2), at 3 weeks prior to chemotherapy. The primary outcome was overall survival (OS). The secondary outcomes included progression-free survival (PFS), pulmonary response, and adverse events (AEs). RESULTS: The final analysis included 95 patients in the chemotherapy group and 41 patients in the combination treatment group. The median OS was 14 months (95 % CI 11.0-17.0) in the chemotherapy group and 19 months (95 % CI 18.0-24.0) in the combination group (P = 0.015). In multivariate Cox regression analysis, DEB-BACE plus chemotherapy was associated with lower risk of death versus chemotherapy only (HR 0.16, 95 % CI 0.05-0.52; log rank test P = 0.003). The median PFS was 6 months (95 % CI 4.0-7.0) in the chemotherapy group and 8 months (95 % CI 6.0-8.0) in the combination group (P = 0.015). The pulmonary objective response rate (ORR) and disease control rate (DCR) were 48.4 % and 62.1 % in chemotherapy group versus 82.9 % and 90.2 % in combination group (P < 0.001 and = 0.001, respectively). AEs occurred in 133 patients (97.8 %). The rate of bone marrow suppression was 48.4 % (46/95) in the chemotherapy group versus 7.3 % (3/41) in the combination group (P < 0.001). CONCLUSION: Compared with chemotherapy alone, DEB-BACE plus chemotherapy was associated with longer survival outcomes and lower rate of bone marrow suppression.

Machine Learning Classifier for Preoperative Prediction of Early Recurrence After Bronchial Arterial Chemoembolization Treatment in Lung Cancer Patients.

RATIONALE AND OBJECTIVES: Bronchial arterial chemoembolization (BACE) was deemed as an effective and safe approach for advanced standard treatment-ineligible/rejected lung cancer patients. However, the therapeutic outcome of BACE varies greatly and there is no reliable prognostic tool in clinical practice. This study aimed to investigate the effectiveness of radiomics features in predicting tumor recurrence after BACE treatment in lung cancer patients. MATERIALS AND METHODS: A total of 116 patients with pathologically confirmed lung cancer who received BACE treatment were retrospectively recruited. All patients underwent contrast-enhanced CT within 2 weeks before BACE treatment and were followed up for more than 6 months. We conducted a machine learning-based characterization of each lesion on the preoperative contrast-enhanced CT images. In the training cohort, recurrence-related radiomics features were screened by least absolute shrinkage and selection operator (LASSO) regression. Three predictive radiomics signatures were built with linear discriminant analysis (LDA), support vector machine (SVM) and logistic regression (LR) algorithms, respectively. Univariate and multivariate LR analyses were performed to select the independent clinical predictors for recurrence. The radiomics signature with best predictive performance was integrated with the clinical predictors to form a combined model, which was visualized as a nomogram. The performance of the combined model was assessed by receiver operating characteristic curve (ROC), calibration curve, and decision curve analysis (DCA). RESULTS: Nine recurrence-related radiomics features were screened out, and three radiomics signatures (RadscoreLDA, RadscoreSVM and RadscoreLR) were built based on these features. Patients were classified into the low-risk and high-risk groups based on the optimal threshold of three signatures. Progression-free survival (PFS) analysis showed that patients of low-risk group achieved longer PFS than patients of high-risk group (P < 0.05). The combined model including RadscoreLDA and independent clinical predictors (tumor size, carcinoembryonic antigen and pro-gastrin releasing peptide) achieved the best predictive performance for recurrence after BACE treatment. It yields AUCs of 0.865 and 0.867 in the training and validation cohorts, with accuracy (ACC) of 0.804 and 0.750, respectively. Calibration curves indicated that the probability of recurrence predicted by the model fits well with the actual recurrence probability. DCA showed that the radiomics nomogram was clinically useful. CONCLUSION: The radiomics and clinical predictors-based nomogram can predict tumor recurrence after BACE treatment effectively, which allowing oncologists to identify potential recurrence and enable better patient management and clinical decision-making.

Postoperative survival of extrahepatic and intrahepatic cholangiocarcinoma after surgery: a population-based cohort.

OBJECTIVES: The study was designed to clarify the difference between extrahepatic cholangiocarcinoma (ECC) and intrahepatic cholangiocarcinoma (ICC) in postoperative cancer-specific death. DESIGN: Patients diagnosed with ECC and ICC after surgery, who are identified from the Surveillance, Epidemiology and End Results programme, are eligible for this retrospective cohort study. SETTING: Survival between groups was compared using the traditional Kaplan-Meier method and the cumulative incidence function (CIF) method. Propensity score-matched (PSM) analysis was conducted to balance the differences in vital variables between groups. The HR and 95% CI for ECC relative to ICC were used to quantify the risk of death. Subgroup analysis was further used to evaluate the stability of the differences between groups. RESULTS: The study included 876 patients with ECC and 1194 patients with ICC. Before PSM, with the Kaplan-Meier method, postoperative overall survival and cancer-specific death for ECC were worse than those for ICC. However, with the CIF method, no difference in postoperative cancer-specific death was found. After PSM, all differences in the considered traits were balanced, and 173 pairs of patients were retained. Survival analysis found that there was no difference in postoperative all-cause death (Kaplan-Meier method, p=0.186) or cancer-specific death (Kaplan-Meier and CIF methods, p=0.500 and p=0.913, respectively), which was consistent with subgroup analysis. CONCLUSIONS: ECC and ICC showed no difference in postoperative cancer-specific death, both in the natural state and in multiple variable-matched conditions. TRIAL REGISTRATION NUMBER: researchregistry4175.

The Preventive Value of Acupoint Sensitization for Patients with Stable Angina Pectoris: A Randomized, Double-Blind, Positive-Controlled, Multicentre Trial.

BACKGROUND: Acupoint sensitization is considered an important factor in the efficacy of acupoint therapy. This study aimed to evaluate the efficacy of acupressure in the prevention of stable angina pectoris using acupoints with different pressure-pain sensitivities. METHODS: A total of 202 patients were enrolled and randomly assigned to a high-sensitivity group (HSG) (n = 109) in which patients received acupressure at the five acupoints with the highest sensitivity to pain and a low-sensitivity group (LSG) (n = 93) in which patients received acupressure at the five acupoints with the lowest sensitivity to pain. The duration of acupressure treatment was 4 weeks, and the patients were evaluated at baseline, week 4, and week 8. The primary outcome was a change in the frequency of angina attacks from baseline. The secondary outcomes included nitroglycerin consumption, the Canadian Cardiovascular Society classification, and the Seattle Angina Questionnaire score. Adverse events such as bleeding and subcutaneous haemorrhage were recorded in both groups. RESULTS: The effect of acupressure compared with baseline on the prevention of angina pectoris in HSG was better than that in LSG at week 4 (incidence rate ratio (IRR): 0.691 and 95% confidence interval (CI): [0.569, 0.839]) and week 8 (IRR: 0.692 and 95% CI: [0.569, 0.839]). No significant difference between groups was found in the frequency of nitroglycerin consumption at week 4 (odds ratio (OR) = 0.863 and 95% CI: [0.147, 5.077]) or week 8 (OR = 1.426 and 95% CI: [0.211, 9.661]). Two themes in the questionnaire showed significantly different changes from baseline between the two groups. Scores on the angina frequency (AF) subscale had changed more from the baseline in the HSG at week 8 than in the LSG (mean difference (MD) = 3.807 and 95% CI: [0.673, 6.942]). Scores on the treatment satisfaction (TS) subscale had also changed more in the HSG than in the LSG at week 4 (MD = 3.651 and 95% CI: [0.327, 7.327]) and week 8 (MD = 4.220 and 95% CI: [0.347, 7.346]). One patient in the LSG reported bruising at the acupoint. No unexpected safety problems arose. CONCLUSIONS: This study showed that acupressure at acupoints with high sensitivity to pain may effectively reduce the frequency of stable angina pectoris episodes. This trial is registered with NCT03975140.

Corrigendum: LncRNA PCAT6 Induces M2 Polarization of Macrophages in Cholangiocarcinoma via Modulating miR-326 and RhoA-ROCK Signaling Pathway.

[This corrects the article DOI: 10.3389/fonc.2020.605877.].

Prediction of tumor response via a pretreatment MRI radiomics-based nomogram in HCC treated with TACE.

OBJECTIVES: To develop and validate a pre-transcatheter arterial chemoembolization (TACE) MRI-based radiomics model for predicting tumor response in intermediate-advanced hepatocellular carcinoma (HCC) patients. MATERIALS: Ninety-nine intermediate-advanced HCC patients (69 for training, 30 for validation) treated with TACE were enrolled. MRI examinations were performed before TACE, and the efficacy was evaluated according to the mRECIST criterion 3 months after TACE. A total of 396 radiomics features were extracted from T2-weighted pre-TACE images, and least absolute shrinkage and selection operator (LASSO) regression was applied to feature selection and model construction. The performance of the model was evaluated by receiver operating characteristic (ROC) curves, calibration curves, and decision curves. RESULTS: The AFP value, Child-Pugh score, and BCLC stage showed a significant difference between the TACE response (TR) and non-TACE response (nTR) patients. Six radiomics features were selected by LASSO and the radiomics score (Rad-score) was calculated as the sum of each feature multiplied by the non-zero coefficient from LASSO. The AUCs of the ROC curve based on Rad-score were 0.812 and 0.866 in the training and validation cohorts, respectively. To improve the diagnostic efficiency, the Rad-score was further integrated with the above clinical indicators to form a novel predictive nomogram. Results suggested that the AUC increased to 0.861 and 0.884 in the training and validation cohorts, respectively. Decision curve analysis showed that the radiomics nomogram was clinically useful. CONCLUSION: The radiomics and clinical indicator-based predictive nomogram can well predict TR in intermediate-advanced HCC and can further be applied for auxiliary diagnosis of clinical prognosis. KEY POINTS: • The therapeutic outcome of TACE varies greatly even for patients with the same clinicopathologic features. • Radiomics showed excellent performance in predicting the TACE response. • Decision curves demonstrated that the novel predictive model based on the radiomics signature and clinical indicators has great clinical utility.

Iodine-125 Brachytherapy Can Prolong Progression-Free Survival of Patients with Locoregional Recurrence and/or Residual Hepatocellular Carcinoma After Radiofrequency Ablation.

Background: Radiofrequency ablation (RFA) for the treatment of hepatocellular carcinoma (HCC) is limited by locoregional recurrence and/or residual tumors caused by incomplete ablation. Iodine-125 (125I) brachytherapy can achieve a high local control rate in solid carcinoma, but few studies have assessed the efficacy of this treatment for locoregional recurrence and/or residual HCC after RFA. Objective: To investigate the effectiveness and safety of 125I brachytherapy for treating locoregional recurrence and/or residual HCC in patients treated with RFA. Methods: Eligible study patients were those with locoregional recurrence and/or residual HCC on abdominal imaging performed 1 month after RFA at this institution between February 2009 and September 2014 retrospectively. Patients were divided into either the control group (no treatment until the tumor progressed) or the treatment group (underwent 125I brachytherapy). Progression-free survival (PFS), overall survival (OS), and complications of 125I brachytherapy were evaluated. Results: A total of 42 patients were included in the final analysis, including 29 in the control group and 13 in the treatment group. A total of 457 125I particles were used (mean 32.8 ± 21.3 mCi per case). The median follow-up time was 25 months. Median PFS was 9 months in the control group and 18 months in the treatment group (p = 0.026). The median OS was 28 months in the control group and 33 months in the treatment group (p = 0.441). There were no major complications observed in patients treated with 125I brachytherapy. Conclusion: Iodine-125 brachytherapy can prolong PFS in patients with locoregional recurrence and/or residual HCC after RFA.

Radiofrequency Ablation (RFA) Combined with Transcatheter Arterial Chemoembolization (TACE) for Patients with Medium-to-Large Hepatocellular Carcinoma: A Retrospective Analysis of Long-Term Outcome.

BACKGROUND The aim of this study was to investigate the prognostic value of radiofrequency ablation (RFA) plus transcatheter arterial chemoembolization (TACE) in hepatocellular carcinoma (HCC) patients with tumor size ranging from 3.0 to 10.0 cm. MATERIAL AND METHODS We retrospectively analyzed data on 201 patients with medium-to-large HCC. According to treatment procedure, the patients were divided into the TACE group (n=124) and the TACE+RFA group (n=77). We recorded data on patient safety, subcapsular hepatic hematoma, large amount of ascites, liver abscess, gallbladder injury, and local skin infection. The overall survival (OS) and progression-free survival (PFS) in the 2 groups were analyzed and compared between groups. RESULTS The median PFS was 4.00 months (3.00-5.00 months) in the TACE group and 9.13 months (6.64-11.62 months) in the TACE+RFA group (P<0.001). Median OS was 12.00 months (8.88-15.13 months) in the TACE group and 27.57 months (20.06-35.08 months) in the TACE+RFA group (P<0.001). In the TACE+RFA group, multivariate Cox regression analysis showed that tumor size ≤5 cm) (HR: 1.952, 95% CI: 1.213-3.143, P=0.006), hepatitis B (HR: 2.323, 95% CI: 1.096-4.923, P=0.028), TACE times (1 or >1) (HR: 1.867, 95% CI: 1.156-3.013, P=0.011), alpha-fetoprotein (AFP) level >200 ng/ml (HR: 2.426, 95% CI: 1.533-3.839, P<0.001), and AST level >40 U/L (HR: 1.946, 95% CI: 1.196-3.166, P=0.007) were independent prognostic factors for overall survival. CONCLUSIONS Combination therapy of TACE with RFA is a safe and effective treatment for patients with medium-to-large HCC, with the long-term beneficial effect of retarding tumor progression and improving PFS and OS.

Drug-eluting beads-transcatheter arterial chemoembolization with or without iodine-125 treatment is effective and tolerable in treating advanced non-small cell lung cancer patients: a pilot study.

BACKGROUND: This study aimed to explore the efficacy and safety of drug-eluting beads-transcatheter arterial chemoembolization (DEB-TACE) with or without iodine-125 (125I) seed implantation in treating advanced non-small cell lung cancer (NSCLC) patients. METHODS: A total of 25 advanced NSCLC patients underwent DEB-TACE were consecutively enrolled, among which 17 cases also received 125I seed implantation post DEB-TACE treatment. Treatment response, overall survival (OS), biochemical indexes and safety profiles were recorded and analyzed. RESULTS: Zero (0.0%), 13 (54.2%), 9 (37.5%) and 2 (8.3%) patients realized complete response (CR), partial response (PR), stable disease (SD) and progression disease (PD) respectively, and the objective response rate (ORR) and disease control rate (DCR) were 54.2% and 91.7%. The median OS was 12.6 (95% CI: 7.8-17.5) months. No difference of treatment response or OS was observed between DEB-TACE treatment alone and DEB-TACE plus 125I seed implantation. Predictive factors analysis revealed that tumor size correlated with worse OS. Besides, chest distress grade and dyspnea grade were decreased after DEB-TACE procedure, while clinical symptoms were not changed after 125I seed implantation. The common adverse events (AEs) were fever (32.0%), pain (12.0%) by DEB-TACE treatment, and common AE was pain (26.7%) by 125I seed implantation. CONCLUSIONS: DEB-TACE with or without 125I seed implantation is effective and tolerable in treating advanced NSCLC patients.

Long Non-Coding RNA PCAT6 Induces M2 Polarization of Macrophages in Cholangiocarcinoma via Modulating miR-326 and RhoA-ROCK Signaling Pathway.

LncRNAs can act crucial roles in multiple tumors including cholangiocarcinoma (CCA). M2 polarization of macrophages is crucial for their biological roles in immunologic tolerance, which is able to induce tumorigenesis. Given that increasing evidence have suggested that lncRNAs could participate in modulating immune cell differentiation and function. Our current study was aimed to identify the underlying mechanism of lncRNA prostate cancer-associated transcript 6 (PCAT6) in CCA progression via regulating M2 macrophage polarization. PCAT6 has been reported as an oncogene in many cancers. In our work, we observed increased expression of PCAT6 in CCA patients. PCAT6 expression in various types of immune cells derived from CCA patients was tested by quantitative real-time PCR (qRT-PCR). It was revealed that PCAT6 was highly expressed in macrophages, which indicated that PCAT6 might regulate the function of macrophages to promote CCA progression. Then, via establishing CCA xenograft mouse model, we found loss of PCAT6 obviously triggered the immune response and reduced the in vivo tumor growth. In addition, overexpression of PCAT6 led to the M2 polarization of THP-1-differentiated macrophages. Moreover, miR-326 was predicted and proved as a target for PCAT6. In addition, down-regulation of PCAT6 repressed M2 polarization of macrophages, which was reversed by miR-326 inhibitors. The increase of PCAT6 induced the accumulation of ROS, mitochondrial and metabolic dysfunction in macrophages and mimics of miR-326 exhibited an opposite process. RohA has been recognized as a significant regulator of immune cell function. In our current work, we observed that RohA function as a downstream target for miR-326. In conclusion, our study highlighted a significant role of PCAT6/miR-326/RohA in immune response of macrophages in CCA and indicated PCAT6 as a potential target of immunotherapy in CCA.

FGFR2-BICC1: A Subtype Of FGFR2 Oncogenic Fusion Variant In Cholangiocarcinoma And The Response To Sorafenib.

Fibroblast growth factor receptor (FGFR) family includes four highly conserved receptor tyrosine kinases. Particularly, FGFR2 has been identified as a potential target for tyrosine kinase inhibitor (TKI) treatment. Except for immunohistochemistry and fluorescence in situ hybridization, next-generation sequencing (NGS) technology represents a novel tool for FGFR2 detection that covers a wide range of fusion genes. In the present work, we present a case of cholangiocarcinoma who had FGFR2-BICC1 rearrangement detected by NGS. A 76-year-old female diagnosed with cholangiocarcinoma underwent four cycles of chemotherapy. The NGS assay showed that the tumor had a FGFR2-BICC1 rearrangement. The patient had a favorable tumor response to sorafenib. Herein, we report the first case with cholangiocarcinoma harboring FGFR2-BICC1 who is sensitive to sorafenib therapy.

Multiple metachronous rare primary malignant tumors: A case report.

Multiple primary malignant tumors (MPMTs) are rarely seen among the patients with malignant neoplasms. Moreover, the existence of five MPMTs in the same patient is an extremely rare phenomenon. In this case, a 42-year-old male patient developed five metachronous MPMTs within 16 years and the duration between each malignant tumor shortened with the progression of the disease. Multidisciplinary treatments were used on this patient and he fought against the cancers until the end of his life. Our report provides us with a new awareness of MPMTs, which should be considered when we come across with cancer patients who develop various unexplainable symptoms after the diagnosis of the first neoplasm.

Recognition of Lung Adenocarcinoma-specific Gene Pairs Based on Genetic Algorithm and Establishment of a Deep Learning Prediction Model.

AIM AND OBJECTIVE: Lung cancer is a disease with a dismal prognosis and is the major cause of cancer deaths in many countries. Nonetheless, rapid technological developments in genome science guarantees more effective prevention and treatment strategies. MATERIALS AND METHODS: In this study, genes were pair-matched and screened for lung adenocarcinomaspecific gene relationships. False positives due to fluctuations in single gene expression were avoided and the stability and accuracy of the results was improved. RESULTS: Finally, a deep learning model was constructed with machine learning algorithm to realize the clinical diagnosis of lung adenocarcinoma in patients. CONCLUSION: Comparing with the traditional methods which takes ingle gene as a feature, the relative difference between gene pairs is a higher order feature, leverage high-order features to build the model can avoid instability caused by a single gene mutation, making the prediction results more reliable.

Iodine-125 Brachytherapy Prophylaxis after Radiofrequency Ablation Cannot Benefit Patients in High Risk of Locoregional Hepatocellular Carcinoma Recurrence.

This study evaluated if iodine-125 brachytherapy prophylaxis after radiofrequency ablation (RFA) prolongs time to recurrence (TTR) and overall survival (OS) of patients in high risk of locoregional hepatocellular carcinoma (HCC) recurrence. 116 patients with total tumor necrosis after RFA were divided into iodine-125 brachytherapy prophylaxis treatment group and control group. The primary endpoint was TTR, and secondary endpoints were OS and treatment-related adverse events. There were no significant differences among the baseline characteristics of two subgroups patients. The mean iodine-125 particles were 29.8 (26.59 ± 12.51 mCi) per patient. The mean follow-up was 25 months, and mean TTR of treatment and control groups were 21.7 and 15.9 months (P = 0.733); mean OS of two subgroups were 41.7 and 40.9 months (P = 0.316). There were no significant differences of 1-, 2-, 3-, 4-and 5-years TTR and OS and patients' immunity pre- and 1 month post-treatment. Extrahepatic metastasis was found to have a statistically significant influence on TTR, and AFP, extrahepatic metastasis were found to have a statistically significant influence on OS by multivariate analysis. There was no major complications and procedure related death. Iodine-125 brachytherapy prophylaxis after RFA can't improve TTR and OS of HCC patients who were in high risk of locoregional tumor recurrence.

Evaluation of the blood supply and efficacy of transcatheter arterial chemoembolization for patients with liver metastasis using 18F-fluorodeoxyglucose positron emission tomography/computed tomography.

Our study aims to evaluate the efficacy of transcatheter arterial chemoembolization in the treatment of patients with liver metastasis using integrated 18F-fluorodeoxyglucose positron emission tomography/computed tomography. A total of 97 liver metastasis patients treated by transcatheter arterial chemoembolization were enrolled in this study. The 18F-fluorodeoxyglucose positron emission tomography/computed tomography images of liver metastasis patients were collected before and after transcatheter arterial chemoembolization treatment. The efficacy of transcatheter arterial chemoembolization for the treatment of liver metastasis was evaluated according to the revised Response Evaluation Criteria in Solid Tumors guidelines. The receiver operating characteristic curve analysis was used to determine cut-off values of 18F-fluorodeoxyglucose positron emission tomography parameters (Tsuvmax, Tsuvmax/Lsuvmax, and Tsuvmax/Lsuvmean) for predicting the efficacy of transcatheter arterial chemoembolization. Progression-free survival and the incidence of postoperative complications were compared. Correlation of Tsuvmax, Tsuvmax/Lsuvmax, and Tsuvmax/Lsuvmean with blood supply and lipiodol deposition in the lesion was analyzed. Among three 18F-fluorodeoxyglucose positron emission tomography parameters, the receiver operating characteristic analysis showed that Tsuvmax/Lsuvmax with a cut-off value of 3.56 was the best predictor of transcatheter arterial chemoembolization efficacy. According to the cut-off value of Tsuvmax/Lsuvmax, liver metastasis patients were divided into the Tsuvmax/Lsuvmax ≤ 3.56 and Tsuvmax/Lsuvmax > 3.56 groups. Compared with the Tsuvmax/Lsuvmax > 3.56 group, the Tsuvmax/Lsuvmax ≤ 3.56 group showed a longer progression-free survival and a lower incidence of postoperative complications. The Tsuvmax, Tsuvmax/Lsuvmax, and Tsuvmax/Lsuvmean in the lesion with abundant blood supply were significantly lower than those in peripheral liver parenchyma, while the Tsuvmax, Tsuvmax/Lsuvmax, and Tsuvmax/Lsuvmean in the lesion with lack of blood supply were significantly higher than those in peripheral liver parenchyma. Spearman correlation analysis indicated that lipiodol deposition in the lesion was positively correlated with the Tsuvmax, Tsuvmax/Lsuvmax, and Tsuvmax/Lsuvmean. The Tsuvmax/Lsuvmax of 18F-fluorodeoxyglucose positron emission tomography/computed tomography may be a good tool for predicting the blood supply and efficacy of transcatheter arterial chemoembolization for patients with liver metastasis.

ShRNA knock-down of CXCR7 inhibits tumour invasion and metastasis in hepatocellular carcinoma after transcatheter arterial chemoembolization.

To investigate the effects of lentiviral vector-mediated shRNA suppressing CXCR7 on tumour invasion and metastasis in hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE). HCCLM3 cell lines were cultured and assigned into the CXCR7-shRNA, negative control (NC) and blank groups. The qRT-PCR and Western blotting were applied to detect the mRNA and protein expressions of CXCR7, CXCR4 and MMP-2 in HCCLM3 cells. Cell proliferation and invasion were evaluated by MTT and Transwell assays. A Buffalo rat model of HCC was established. Fifty model rats were divided into the CXCR7-shRNA + TACE, CXCR7-shRNA, TACE, NC and control groups. Immunohistochemistry was performed to detect the expressions of CXCR7, MMP-2, vascular endothelial growth factor (VEGF) and intratumoral CD31-positive vessel count in tumour tissues of mice. Compared with the blank and NC groups, the mRNA and protein expressions of CXCR7 and MMP-2 were decreased in the CXCR7-shRNA group. The cell proliferation and invasion rates of the CXCR7-shRNA group were lower than the blank and NC groups. At the 4th week after TACE, tumour weight of the CXCR7-shRNA + TACE group increased continuously. The CXCR7-shRNA + TACE group showed longer survival time and smaller tumour sizes than other groups. Compared with other groups, the CXCR7-shRNA + TACE and CXCR7-shRNA groups had less number of lung metastatic nodules and lower expressions of CXCR7, MMP-2, VEGF and CD31-positive vessel count. CXCR7-shRNA inhibits tumour invasion and metastasis to improve the efficacy of TACE in HCC by reducing the expressions of CXCR7, MMP-2 and VEGF.

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.

The incidence and outcome of major complication following conventional TAE/TACE for hepatocellular carcinoma.

To investigate the incidence and outcome of major complication following conventional transarterial embolization/chemoembolization (TAE/TACE) therapy for hepatocellular carcinoma (HCC).From May 2010 to May 2016, all patients with major complication following conventional TAE/TACE for HCC were included. Major complication was defined as admission to a hospital for therapy, an unplanned increase in the level of care, prolonged hospitalization, permanent adverse sequelae, or death after conventional TAE/TACE therapy by Society of Interventional Radiology.During the study period, a total of 2863 TAE/TACE procedures were performed among 1120 patients, and a total of 24 patients (21 male and 3 female) developed major complication with the incidence of 2.1% (24/1120) per patient and 0.84% (24/2863) per TAE/TACE procedure. The major complications were liver rupture (n = 6), liver abscess (n = 5), femoral artery pseudoaneurysm (n = 3), cholecystitis (n = 2), biloma (n = 2), pulmonary embolism (n = 2), and 1 each of the following: cerebral lipiodol embolism, tumor lysis syndrome, partial intestinal obstruction, gallbladder perforation. The mean interval from last TAE/TACE procedure to the diagnosis of major complication was 11.1 ±â€Š7.7 days. The treatments of the complications were conservative treatment (n = 12), conservative treatment plus percutaneous drainage (n = 3), ultrasound-guided thrombin injection (n = 3), conservative treatment plus TAE (n = 2), and conservative treatment plus surgery (n = 2). Of the 24 patients, 20 patients were recovered, and remaining 4 patients were died of major complications; therefore, the mortality rate of major complication was 16.7% (4/24).Major complication following conventional TAE/TACE therapy is uncommon; the outcomes are benign of most major complications, but some are mortality.

Regulatory T cells, especially ICOS+ FOXP3+ regulatory T cells, are increased in the hepatocellular carcinoma microenvironment and predict reduced survival.

Hepatocellular carcinoma (HCC) is a common malignant tumour, especially in Asia. Its prognosis is poor, and there are limited methods for predicting patient survival. This study was carried out to analyse the prognostic value of tumour-infiltrating lymphocytes (TILs), especially regulatory T cells (Tregs), in HCC patients. TILs were analysed in 57 randomly selected HCC patients. The prognostic effects of groups with high and low numbers were evaluated by the Kaplan-Meier and Cox model analyses. Although higher densities of CD3+, CD4+, and CD8+ cytotoxic lymphocytes (CTLs) as well as CD56+ NK cells and CD68+ macrophages were observed in peritumoural tissue, increased numbers of forkhead/winged helix transcription factor P3+ (FOXP3+) Tregs were found in intratumoural tissue. Additionally, regarding ICOS+ FOXP3+ Tregs, an increased prevalence in carcinoma was not only associated with the absolute number but also with the percentage of FOXP3+ cells. Higher Treg levels in tumour tissues indicated a worse prognosis, and the FOXP3+ Tregs/CD4+ T cells ratio was an independent prognostic factor for OS. Therefore, FOXP3+ Tregs, especially ICOS+ FOXP3+ Tregs, contribute to the immunosuppressive HCC microenvironment. High tumour-infiltrating Tregs are thought to be an unfavourable prognostic indicator of HCC.

Shikonin potentiates the effect of arsenic trioxide against human hepatocellular carcinoma in vitro and in vivo.

Hepatocellular carcinoma (HCC) is a highly lethal malignancy mostly because of metastasis, recurrence and acquired resistance to conventional chemotherapy. Arsenic trioxide (ATO) is successfully used to treat hematological malignancies, and has been proven to trigger apoptosis in HCC cells. However, the phase II trial evaluating the efficacy and toxicity of ATO in patients with HCC showed that single-agent ATO is poorly active against HCC. Therefore, it is of great importance to develop effective chemosensitization agents to ATO. The aim of the present study was to determine whether shikonin (SHI), a natural product from the root of lithospermum erythrorhizon, could synergistically enhance the anti-HCC efficacy of ATO both in vitro and in vivo. We found that the combination of SHI and ATO exhibited synergistic anticancer efficacy and achieved greater selectivity between cancer cells and normal cells. By inducing intracellular oxidative stress, SHI potentiated ATO-induced DNA damage, followed by increased activation of endoplasmic reticulum stress. In addition, inhibition of ROS reversed the apoptosis induced by SHI and ATO, and recovered the activation of endoplasmic reticulum stress, which revealed the vital role of ROS in the synergism. Moreover, HepG2 xenograft tumor growth in nude mice was more effectively inhibited by combined treatment with SHI and ATO. These data suggest that the combination of SHI with ATO presents a promising therapeutic approach for the treatment of HCC.