A Changing Paradigm for the Treatment of Intermediate-Stage Hepatocellular Carcinoma: Asia-Pacific Primary Liver Cancer Expert Consensus Statements.

The Asia-Pacific Primary Liver Cancer Expert (APPLE) Consensus Statement on the treatment strategy for patients with intermediate-stage hepatocellular carcinoma (HCC) was established on August 31, 2019, in Sapporo, Hokkaido during the 10th Annual APPLE Meeting. This manuscript summarizes the international consensus statements developed at APPLE 2019. Transarterial chemoembolization (TACE) is the only guideline-recommended global standard of care for intermediate-stage HCC.

CYP2C19 polymorphism has no influence on rabeprazole-based hybrid therapy for eradication.

Aim: To evaluate the impact of cytochrome P450 2C19 (CYP2C19) and interleukin-1β (IL-1β) polymorphisms on the efficacy of () eradication by using rabeprazole-based hybrid therapy.

Methods: A total of 88 -infected patients were recruited to receive 14-d of hybrid therapy from March 2013 to May 2014. Three patients were excluded from analysis because of incomplete compliance.

Niemann-Pick Type C2 Protein Regulates Free Cholesterol Accumulation and Influences Hepatic Stellate Cell Proliferation and Mitochondrial Respiration Function.

Liver fibrosis is the first step toward the progression to cirrhosis, portal hypertension, and hepatocellular carcinoma. A high-cholesterol diet is associated with liver fibrosis via the accumulation of free cholesterol in hepatic stellate cells (HSCs). Niemann-Pick type C2 (NPC2) plays an important role in the regulation of intracellular free cholesterol homeostasis via direct binding with free cholesterol.

Glycine N-methyltransferase deficiency in female mice impairs insulin signaling and promotes gluconeogenesis by modulating the PI3K/Akt pathway in the liver.

Background: Glycine N-methyltransferase (GNMT) is abundantly expressed in the normal liver but is down-regulated in liver cancer tissues. GNMT knockout (Gnmt-/-) mice can spontaneously develop chronic hepatitis, fatty liver, and liver cancer. We previously demonstrated that hepatic GNMT is decreased in high-fat-diet-induced type 2 diabetes mellitus, but its contribution to metabolic syndrome is unclear.

Niemann-Pick Type C2 Protein Mediates Hepatic Stellate Cells Activation by Regulating Free Cholesterol Accumulation.

In chronic liver diseases, regardless of their etiology, the development of fibrosis is the first step toward the progression to cirrhosis, portal hypertension, and hepatocellular carcinoma. Hepatic stellate cells (HSCs) are the main profibrogenic cells that promote the pathogenesis of liver fibrosis, and so it is important to identify the molecules that regulate HSCs activation and liver fibrosis. Niemann-Pick type C2 (NPC2) protein plays an important role in the regulation of intracellular cholesterol homeostasis by directly binding with free cholesterol.

Hybrid vs sequential therapy for eradication of Helicobacter pylori in Taiwan: A prospective randomized trial.

Aim: To evaluate the efficacy of sequential vs hybrid therapy in patients with Helicobacter pylori (H. pylori) infection.

Methods: From March 2013 to May 2014, one hundred and seventy-five H.

Performance of Routine Helicobacter pylori Invasive Tests in Patients with Dyspepsia.

Background. This study was designed to compare the accuracy of three different invasive methods for the detection of Helicobacter pylori (H. pylori) infection in patients with dyspepsia.

Characterization of Niemann-Pick Type C2 protein expression in multiple cancers using a novel NPC2 monoclonal antibody.

Niemann-Pick Type C2 (NPC2) plays an important role in the regulation of intracellular cholesterol homeostasis via direct binding with free cholesterol. However, little is known about the significance of NPC2 in cancer. In this study, we have pinpointed the impact of various different cancers on NPC2 expression.

Glycine N-methyltransferase deficiency affects Niemann-Pick type C2 protein stability and regulates hepatic cholesterol homeostasis.

Nonalcoholic fatty liver disease (NAFLD) is associated with the development of metabolic syndromes and hepatocellular carcinoma (HCC). Cholesterol accumulation is related to NAFLD, whereas its detailed mechanism is not fully understood. Previously, we reported that glycine N-methyltransferase (GNMT) knockout (Gnmt(-/-)) mice develop chronic hepatitis and HCC.

Deficiency of glycine N-methyltransferase results in deterioration of cellular defense to stress in mouse liver.

Purpose: Previously, we reported that glycine N-methyltransferase (GNMT) interacts with benzo[a]pyrene (BaP) and inhibits BaP-DNA adducts formation. In addition, Gnmt knockout (Gnmt(-/-)) mice developed chronic hepatitis and hepatocellular carcinoma (HCC). The aims of this study were to understand the gene expression profile of Gnmt(-/-) mice and to study the interaction between BaP and GNMT deficiency in vivo.

Neuroprotective activity of Vitis thunbergii var. taiwaniana extracts in vitro and in vivo.

Vitis thunbergii var. taiwaniana (VTT) is a wild grape native to Taiwan, where it has been used as a folk medicine. In this study, we found that the branch and leaf ethanol extracts of VTT significantly inhibited the inducible nitric oxide (NO) synthase protein expression and NO production in BV2 microglia.

Serum prohepcidin levels correlate with hepatic iron stores in chronic hepatitis C patients.

Background/aims: Increased serum iron indices and hepatic iron stores are frequent in patients with chronic hepatitis C (CHC). The antimicrobial peptide hepdicin produced in the liver plays a pivotal role in iron homeostasis.

Methodology: To determine the expression of hepcidin, the serum levels of prohepcidin were measured in 58 CHC patients and 144 healthy controls.

Effects of oral administration of yam tuber storage protein, dioscorin, to BALB/c mice for 21-days on immune responses.

Dioscorin, the tuber storage protein of yam, was reported to have immunomodulatory activity in RAW264.7 murine macrophage cell lines ( Food and Chemical Toxicology , 2007 , 45 , 2312 -2318 ). However, the immunomodulatory function of dioscorin after being ingested was not elucidated in vivo.

Osthole, a potential antidiabetic agent, alleviates hyperglycemia in db/db mice.

Osthole is an agent isolated from Cnidium monnieri (L.) Cusson and Angelica pubescens and has been used to treat several diseases, including metabolic syndromes. To investigate the hypoglycemic effects of osthole in diabetic db/db mice and the underlying mechanisms of these effects by in vitro assay, diabetic db/db mice and cell experiments were utilized to understand its possible effects.

Relationship between electrolytes and heart rate variability parameters in end-stage renal failure patients before and after hemodialysis.

Objective: One of the major causes of death in end-stage renal disease (ESRD) patients under maintenance hemodialysis (HD) is ventricular arrhythmias (VA). Heart rate variability (HRV) has been claimed to be related to disturbance of autonomic nervous system and therefore a predictor for VA occurrence. The purpose of this study is to evaluate the relationship between the HRV parameters and electrolytes before and after hemodialysis in ESRD patients.

Immunomodulatory activity of dioscorin, the storage protein of yam (Dioscorea alata cv. Tainong No. 1) tuber.

The purified dioscorin from yam (Dioscorea alata L. cv. Tainong 1) tuber was previously reported (Hsu et al.

Involvement of fatty acid-CoA ligase 4 in hepatocellular carcinoma growth: roles of cyclic AMP and p38 mitogen-activated protein kinase.

Aim: Fatty acid-CoA ligase 4 (FACL4) is an arachidonate-preferring enzyme which has been shown to be up-regulated in human colon cancer tissues and implicated in the colon tumorigenesis. The purpose of this study was to investigate the role of FACL4 in the human hepatocellular carcinoma (HCC) tumorigenesis and the specific signal pathways involved in this process.

Methods: We investigated the expression and regulation of FACL4 in HCC, adjacent non-tumorous liver tissues, and cell lines.

Cytochrome C release induces apoptosis of nasopharyngeal carcinoma (NPC) by antitumor glyfoline.

The mechanism of action, leakage of cytochrome c from mitochondria into cytosol, for the antineoplastic compound glyfoline was examined. Additionally, our current studies revealed that glyfoline induced apoptotic changes and arrested cell cycle procession at the G2/M phase in nasopharyngeal carcinoma (NPC). A reverse transcriptase polymerase chain reaction (RT-PCR) showed no specific changes of apoptosis-related gene expression (i.

MDM2 expression in EBV-infected nasopharyngeal carcinoma cells.

To understand whether the p53-regulated mdm2 gene expression was altered by the Epstein-Barr virus (EBV) in nasopharyngeal carcinoma (NPC), the NPC-TW01 cell line was infected by EBV through IgA receptor-mediated endocytosis. The mdm2 gene was expressed only in a small fraction of the NPC cell population and could be enhanced in the EBV-infected (EBV+) cells. In the animals bearing EBV+ and EBV- NPC xenografts, the MDM2+ cells only appeared in clusters in both EBV+ and EBV- tumors with stronger expression in EBV+ cells.

Carbon dioxide-enhanced sonographically guided percutaneous ethanol injection: treatment of patients with viable and recurrent hepatocellular carcinoma.

Objective: Viable portions of tumors can persist and recurrent tumors sometimes appear in patients with hepatocellular carcinoma who have undergone transcatheter arterial chemoembolization, percutaneous ethanol injection, or a combination of the two. Some of these tumors are difficult to treat or do not respond to additional treatment using the same protocol. In this article, we examine the use of carbon dioxide (CO(2))-enhanced sonographically guided percutaneous ethanol injection to treat patients with such tumors.

Long-term survival of Taiwanese patients with hepatocellular carcinoma after combination therapy with transcatheter arterial chemoembolization and percutaneous ethanol injection.

Background And Purpose: Several studies have shown a superior effect of combination therapy with transcatheter arterial chemoembolization (TACE) and percutaneous ethanol injection (PEI) compared with either monotherapy for the treatment of advanced hepatocellular carcinoma (HCC), but there have been no reports on combination treatment from Taiwan. This study investigated the long-term survival and prognostic factors of HCC patients treated with TACE/PEI combination therapy.

Methods: A total of 153 consecutive HCC patients, with tumor sizes between 2 and 3 cm in 47 patients, between 3 and 5 cm in 66 patients, and between 5 and 13 cm in 40 patients, who received TACE/PEI combination therapy were included in this retrospective study.

Genotypic and phenotypic characterization of a putative tumor susceptibility gene, GNMT, in liver cancer.

Glycine N-methyltransferase (GNMT), a multifunctional protein involved in the maintenance of the genetic stability, is often down-regulated in hepatocellular carcinoma (HCC). Using genotypic characterization of GNMT in hepatoma cell lines and in a Taiwanese population with a high incidence of liver cancer we have investigated the role of this gene in the progression of liver cancer. Six novel polymorphisms, including two short tandem repeats, one 4-nucleotide insertion/deletion polymorphism, and three single nucleotide polymorphisms, in GNMT were identified in this study.

Assessment of vascularity in hepatic tumors: comparison of power Doppler sonography and intraarterial CO(2)-enhanced sonography.

Objective: The purpose of the study was to compare power Doppler sonography with intraarterial CO(2)-enhanced sonography for revealing vascularity in treated and untreated hepatic tumors.

Subjects And Methods: Fifty-five patients with 93 liver tumors were prospectively examined with power Doppler sonography and CO(2)-enhanced sonography. These tumors included 29 hepatocellular carcinomas in patients with no previous treatment, 26 treated hepatocellular carcinomas, and 38 hemangiomas.