Kaplan-Meier survival curve in patients diagnosed with intermediate-stage hepatocellular carcinoma.

<p>A: the day from the last TACE (any patient), B: the day from the last TACE (patients deemed as TACE refractory/failure), and C: the day from the point of being diagnosed with intermediate-stage HCC.</p

Baseline demographic data and patient characteristics at the time of being diagnosed with intermediate-stage hepatocellular carcinoma.

<p>Baseline demographic data and patient characteristics at the time of being diagnosed with intermediate-stage hepatocellular carcinoma.</p

Kaplan–Meier survival curve in advanced-stage hepatocellular carcinoma patients receiving sorafenib.

<p>Kaplan–Meier survival curve in advanced-stage hepatocellular carcinoma patients receiving sorafenib.</p

Baseline demographic data and patient characteristics when starting sorafenib.

<p>Baseline demographic data and patient characteristics when starting sorafenib.</p

Multivariate analysis of survival in sorafenib-treated patients with intermediate-stage hepatocellular carcinoma.

<p>Multivariate analysis of survival in sorafenib-treated patients with intermediate-stage hepatocellular carcinoma.</p

Kaplan–Meier survival curve in intermediate-stage hepatocellular carcinoma patients receiving sorafenib.

<p>Kaplan–Meier survival curve in intermediate-stage hepatocellular carcinoma patients receiving sorafenib.</p

Identification of BMI1 Promoter Inhibitors from <i>Beaumontia murtonii</i> and <i>Eugenia operculata</i>

B-Cell-specific Moloney murine leukemia virus insertion region 1 (BMI1) is a core component of the polycomb repressive complex 1 (PRC1). Abnormal expression of BMI1 is associated with a number of human malignances and cancer stem cells (CSCs), which cause chemotherapy resistance. Therefore, small molecules that inhibit BMI1 expression are potential candidates for cancer therapy. In this study, a cell-based reporter gene assay was developed that allowed BMI1 promoter activity to be measured in 293T human embryonic kidney cells based on luciferase expression levels. Using this screening assay, the methanol-soluble extracts of <i>Beaumontia murtonii</i> and <i>Eugenia operculata</i> were selected as leads. Bioassay-guided fractionation of the extracts led to the isolation of three known cardenolides (<b>1</b>–<b>3</b>) and one new compound (<b>4</b>) from <i>B. murtonii</i> and two known triterpenoids (<b>5</b> and <b>6</b>) and one new compound (<b>7</b>) from <i>E. operculata</i>. These seven compounds inhibited BMI1 promoter activity (IC₅₀ range 0.093–23.0 μM), and the most active compound, wallichoside (<b>1</b>), was further evaluated. Western blot analysis revealed that wallichoside (<b>1</b>) decreases BMI1 protein levels in HCT116 human colon carcinoma cells, and flow cytometry analysis showed that it significantly reduced levels of the CSC biomarker epithelial cell adhesion molecule. Wallichoside (<b>1</b>) also inhibited sphere formation of Huh7 human hepatocellular carcinoma cells, indicating that it diminished the self-renewal capability of CSCs

A Prognostic Score for Patients with Intermediate-Stage Hepatocellular Carcinoma Treated with Transarterial Chemoembolization

<div><p>Background</p><p>Intermediate-stage hepatocellular carcinoma (HCC), defined according to the Barcelona Clinic Liver Cancer (BCLC) staging system, is a heterogeneous condition with variable clinical benefits from transarterial chemoembolization (TACE). This study aimed to develop a simple validated prognostic score based on the predictive factors for survival in patients with intermediate-stage HCC treated with TACE.</p><p>Methods</p><p>Three-hundred and fifty patients with intermediate-stage HCC undergoing initial TACE at Chiba University Hospital (training cohort; <i>n</i> = 187) and two affiliated hospitals (validation cohort; <i>n</i> = 163) were included. Following variables were entered into univariate and multivariate Cox regression models to develop a points-based clinical scoring system: gender, age, etiology, pretreatment, Child–Pugh score, aspartate aminotransferase, creatinine, C-reactive protein, alfa-fetoprotein, size of the largest lesion, and number and location of lesions.</p><p>Results</p><p>The number of lesions and the Child–Pugh score were identified as independent prognostic factors in the training cohort. The development of a 0–7-point prognostic score, named the Chiba HCC in intermediate-stage prognostic (CHIP) score, was based on the sum of three subscale scores (Child–Pugh score = 0, 1, 2, or 3, respectively, number of lesions = 0, 2, or 3, respectively, HCV-RNA positivity = 0 or 1, respectively). The generated scores were then differentiated into five groups (0–2 points, 3 points, 4 points, 5 points, and 6–7 points) by the median survival time (65.2, 29.2, 24.3, 13.1, and 8.4 months, respectively; <i>p</i> < 0.0001). These results were confirmed in the external validation cohort (<i>p</i> < 0.0001).</p><p>Conclusions</p><p>The CHIP score is easy-to-use and may assist in finding an appropriate treatment strategy for intermediate-stage HCC.</p></div

Impact of Radiofrequency Ablation-Induced Glisson’s Capsule-Associated Complications in Patients with Hepatocellular Carcinoma

<div><p>Background</p><p>Radiofrequency ablation (RFA) is commonly used to locally treat hepatocellular carcinoma (HCC). However, when tumors are close to the Glisson’s capsule, RFA may induce injury in this region, complicating therapeutic efforts. We investigated the impact of RFA-induced Glisson’s capsule-associated complications on liver function and prognosis of HCC patients.</p><p>Methods</p><p>We retrospectively reviewed our patient database and found 170 early-stage HCC patients treated via RFA from April 2004 to December 2012. We defined RFA-induced Glisson’s capsule-associated complication as lasting hepatic arterioportal (AP) fistula, major intrahepatic bile-duct dilatation (affecting two or more subsegments), or hepatic infarction. We also defined liver failure as initial occurrence of either total bilirubin increase (>3.0 mg/dL), uncontrolled ascites, or encephalopathy.</p><p>Results</p><p>In our cohort, 15 patients had RFA-induced Glisson’s capsule-associated complications (incidence of related complications, with some overlap: lasting AP fistula, n = 9; major intrahepatic bile-duct dilatation, n = 7; and hepatic infarction, n = 2). The cumulative incidence of liver failure before stage progression was significantly higher and the median overall survival (OS) was significantly lower (52.3 months) in HCC patients with Glisson’s capsule-associated complications than in those without Glisson’s capsule-associated complications (95.0 months). In addition, multivariate analysis demonstrated that Glisson’s capsule-associated complication was a significant independent factor associated with OS.</p><p>Conclusions</p><p>In this study, we have shown that early-stage HCC patients with RFA-induced Glisson’s capsule-associated complications may have higher risks in poor prognosis.</p></div

Concordance index (C-index) for each scoring model in the training set.

<p>Abbreviations: CHIP score, Chiba hepatocellular carcinoma in intermediate-stage prognostic score; HAP score, hepatoma arterial-embolisation prognostic score.</p><p>Concordance index (C-index) for each scoring model in the training set.</p