Dose-dependent Effects of Cacao Polyphenol Intake on Lipid Metabolism in Rats.

Cacao polyphenols (CPs) are known to suppress the oxidation of low-density lipoprotein and cholesterol absorption. Herein, we examined the impact of CP on the lipid metabolism in rats fed CP-rich chocolate, by analyzing liver weight and histology, via hematoxylin-eosin staining. The high-CP group had significantly lighter livers than the CP-free group. Histologically, the high-CP group showed significantly lower liver fat accumulation than the CP-free group. These results suggest that CPs prevent liver fat accumulation, being potentially useful against obesity and related diseases.

Efficacy of endobronchial ultrasound-guided transbronchial biopsy without guide sheath for small peripheral pulmonary lesions (≤15 mm): A retrospective cohort study.

INTRODUCTION: Endobronchial ultrasonography-guided transbronchial biopsy (EBUS-TBB) with guide sheath (GS) is an effective procedure for diagnosing small peripheral pulmonary lesions (PPLs) (≤20 mm in the largest diameter). However, samples obtained using EBUS-TBB with GS are small, and the diagnostic yield of small PPLs biopsied using EBUS-TBB with GS is unsatisfactory. OBJECTIVES: The aim of this study was to evaluate the diagnostic yield of small PPLs using EBUS-TBB without GS compared to that with GS. MATERIALS AND METHODS: Between 1 April 2013 and 31 March 2015, 276 consecutive lesions were biopsied using EBUS-TBB with GS or without GS. We retrospectively compared EBUS-TBB with and without GS in terms of the diagnostic yield and complications related to small PPLs (≤20 mm). RESULTS: Of the 276 lesions who underwent EBUS-TBB with or without GS, we identified 80 lesions with small PPLs (≤20 mm). Sixty-two lesions were successfully diagnosed by EBUS-TBB (77.5%, diagnostic yield). The diagnostic yield of PPLs using EBUS-TBB without GS was not significantly higher than that using EBUS-TBB with GS (34/41 = 82.9% and 28/39 = 71.7%, respectively; p = 0.233). However, according to size (≤15 mm or > 15 mm), location (upper, middle/lingular, or lower area), and structure (solid nodule or ground-glass opacity), the diagnostic yield of small PPLs (≤15 mm) using EBUS-TBB without GS was significantly higher than with GS (21/26 = 80.7% vs. 8/16 = 50.0%, p = 0.036). There were no complications among the two groups. CONCLUSIONS: EBUS-TBB without GS is an effective and safe procedure for diagnosing small PPLs (≤15 mm) compared to that with GS.

An Imbalance in TAZ and YAP Expression in Hepatocellular Carcinoma Confers Cancer Stem Cell-like Behaviors Contributing to Disease Progression.

Transcriptional coactivator with PDZ-binding motif (TAZ) and yes-associated protein (YAP) are equivalently placed downstream effectors of the Hippo pathway with oncogenic roles in human cancers. However, the expression profiles of TAZ/YAP differ depending on the cancer cell type, suggesting that these proteins have different roles during cancer progression, yet no studies have examined the biologic significance of the balance between TAZ and YAP expression levels. Here we examined the functional roles of TAZ/YAP in hepatocellular carcinoma progression. We found that TAZ, but not YAP, was predominantly expressed in HCC. TAZ knockdown under normal conditions attenuated cell growth in HCC cells; however, TAZ knockdown combined with 5-fluorouracil treatment significantly increased chemoresistance compared with control cells. Notably, TAZ knockdown induced compensatory YAP expression and was accompanied by upregulation of CD90, a HCC-specific cancer stem cell marker. Continuous treatment with 5-fluorouracil also induced YAP expression and promoted tumor formation in vivo. Conversely, double knockdown of TAZ/YAP reduced chemoresistance and tumorigenicity. Moreover, YAP knockdown aggravated HCC cell growth to a greater degree than TAZ knockdown, and YAP overexpression was strongly associated with poor prognoses in patients with HCC. Collectively, these studies demonstrate that TAZ and YAP exhibit different functional roles in cancer progression, and a shift to predominant YAP expression upon TAZ depletion conferred cancer stem cell-like properties including chemoresistance and tumorigenicity in HCC. Therefore, targeting of both TAZ/YAP will be required for a complete antitumor response in HCC.

EZH2 is associated with malignant behavior in pancreatic IPMN via p27Kip1 downregulation.

BACKGROUND: The epigenetic mechanism of tumorigenesis in pancreatic intraductal papillary mucinous neoplasm (IPMN) remains largely unknown. The aim of this study is to examine the role of enhancer of zeste homologue 2 (EZH2) alteration in pancreatic IPMN progression. METHODS: Fifty-four surgically resected pancreatic IPMN specimens, including a total of 181 lesions (normal duct in 48, adenoma in 50, borderline atypia in 53, carcinoma in situ (CIS) in 19, and invasive carcinoma in 11) were analyzed by immunohistochemical staining (EZH2, Ki-67, p27Kip1). Using paraffin embedded sections, total RNA was successfully extracted from 20 IPMN lesions (borderline IPMN in 9, CIS in 6, invasive carcinoma in 5) and 7 pancreatic normal ducts, and then levels of EZH2 and p27Kip1 mRNA were analyzed by real time PCR. RESULTS: In immunohistochemical analysis, cell proliferative activity revealed by Ki-67 positive nuclei was increased during IPMN progression (normal duct