Targeting FROUNT with disulfiram suppresses macrophage accumulation and its tumor-promoting properties.

Tumor-associated macrophages affect tumor progression and resistance to immune checkpoint therapy. Here, we identify the chemokine signal regulator FROUNT as a target to control tumor-associated macrophages. The low level FROUNT expression in patients with cancer correlates with better clinical outcomes. Frount-deficiency markedly reduces tumor progression and decreases macrophage tumor-promoting activity. FROUNT is highly expressed in macrophages, and its myeloid-specific deletion impairs tumor growth. Further, the anti-alcoholism drug disulfiram (DSF) acts as a potent inhibitor of FROUNT. DSF interferes with FROUNT-chemokine receptor interactions via direct binding to a specific site of the chemokine receptor-binding domain of FROUNT, leading to inhibition of macrophage responses. DSF monotherapy reduces tumor progression and decreases macrophage tumor-promoting activity, as seen in the case of Frount-deficiency. Moreover, co-treatment with DSF and an immune checkpoint antibody synergistically inhibits tumor growth. Thus, inhibition of FROUNT by DSF represents a promising strategy for macrophage-targeted cancer therapy.

Concurrent Use of Conventional Drugs with Chinese Herbal Products in Taiwan: A Population-based Study.

The increased use of Chinese herbal products (CHPs) worldwide has raised the concern of herb-drug interactions. The aim of this study was to determine the prevalence and utilization patterns of concurrent use of conventional drugs and CHPs in Taiwan. The usage and frequency of services in the co-prescription of a CHP and a conventional drug were evaluated. Subjects were recruited from a simple random sample of 1,000,000 subjects from over 22 million beneficiaries of the National Health Insurance in 2007. The logistic regression method was employed to estimate the odds ratios (ORs) for the co-prescription of a CHP and a conventional drug (CH + D) and a conventional drug alone (D-alone). The prevalence of the CH + D was 14.1%. Females, regular salary earners, and elderly (65 years and above) were more likely to consume a CHP and a conventional drug concurrently. Painkillers, especially acetaminophen, and anti-cough medicines were the top two conventional drugs that were most frequently co-prescribed with a CHP. Anti-cough medication is the most common conventional drug co-prescribed with CHP, after painkillers. We recommend that safety issues be investigated in future research and integrating both healthcare technologies may be beneficial for the overall health and quality of life of patients.

The risk factors for ultrasound-diagnosed non-alcoholic fatty liver disease among adolescents.

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is garnering increasing interest and acceptance as one of the most important causes of chronic liver disease. The aim of this study was to investigate the risk factors for NAFLD among selected adolescent students in Hualien City, Taiwan. MATERIALS AND METHODS: A stratified random sampling scheme was carried out among 1724 adolescent students aged 12 or 13 years old in Hualien City. In total, 220 students (normal: overweight: obese = 97:48:75) agreed to join the study. They underwent physical examination, laboratory tests and ultrasonography examination of the liver. Diagnosis of NAFLD in this study was based on sonographic evidence of a fatty liver and testing negative for serum HBsAg and anti- HCV antibody. RESULTS: Of the 220 participants, 4 were excluded because they tested positive for HBsAg or anti-HCV antibody. NAFLD was detected in 86 (39.8%) out of the 216 subjects. The rate of NAFLD in the adolescents increased progressively from 16.0% in the normal group to 50.5% in the overweight group, and 63.5% among the obese subjects. Compared to their normal counterparts, adolescents with NAFLD had a significantly higher weight, body mass index (BMI), waist circumference, levels of alanine aminotransferase (ALT), triglyceride and nonhigh- density-lipoprotein (non-HDL) cholesterol. However, among the participants with NAFLD, only 20 (23.3%) showed ALT abnormality but there was an increasing trend of ALT abnormality as the severity of fatty liver increased. In addition, the higher ALT, Homeostasis model assessment- insulin resistance (HOMA-IR), cholesterol, triglyceride, and non-HDL levels and lower HDL-C as the severity of fatty liver increased. In a stepwise logistic regression analysis, the most significant factor associated with the presence of NAFLD was weight category. When compared with their normal counterparts, overweight and obese adolescents had a 4.14 and 5.98 times the risk of having NAFLD, respectively. Elevated ALT was the second most important factor as adolescents with elevated ALT were more likely to have NAFLD (odds ratio = 3.32, 95% CI: 1.16 to 9.50). Non-HDL cholesterol level was the third most important factor associated with NAFLD with a 3.81-fold increase in risk incurred for every l n (1 mg/dL) increment. CONCLUSIONS: Obesity, ALT abnormality and elevated non-HDL-cholesterol are risk factors for NAFLD in adolescents. However, only 23.3% of the adolescents with NAFLD showed an abnormality for ALT. Therefore, ALT alone is not a sufficient indicator; and it is recommended that ultrasonography of the liver should be part of the routine health examination of obese adolescents.

Etiology of acute pancreatitis--a multi-center study in Taiwan.

BACKGROUND/AIMS: Little is known about the etiology of acute pancreatitis in Taiwan. The aim of this study was to evaluate the current etiology of acute pancreatitis in Taiwan by a multi-center cooperative study. METHODOLOGY: Patients with acute pancreatitis were collected from 8 major leading hospitals located at northern, southern, middle and eastern Taiwan from July 1, 1998 to June 30, 2000. The diagnosis of acute pancreatitis was based on characteristic clinical signs and symptoms and three-fold elevation of serum amylase/lipase level or positive evidence in imaging studies. The etiology was attributed to alcohol, gallstones, hypertriglyceridemia, miscellaneous causes, and idiopathic causes. RESULTS: In total 1,193 patients with acute pancreatitis were identified. There were 852 (71.4%) men and 341 (28.6%) women with a mean age of 52.5 years, ranging from 9 to 100 years. Etiology was identified as alcohol in 423 (33.6%), gallstones in 407 (34.1%), hypertriglyceridemia in 147 (12.3%), miscellaneous causes in 109 (9.1%), and idiopathic causes in 107 (9.0%). Patients with alcohol-related acute pancreatitis were the youngest (mean age: 41.5 years), while those with gallstone pancreatitis were the eldest (mean age: 64.1 years) (p < 0.001). The predominant cause of acute pancreatitis in women is gallstones, while alcohol is the leading cause of acute pancreatitis in Taiwanese males. In northern Taiwan, gallstone is the major cause of acute pancreatitis, while alcohol is the predominant etiology in middle, southern, and eastern Taiwan. CONCLUSIONS: Alcohol has become the predominant cause of acute pancreatitis in Taiwan recently. Ecological and gender differences play important roles in the etiology of acute pancreatitis in Taiwan.