Peginterferon alfa-2a plus ribavirin for hemophilic patients with chronic hepatitis C virus infection in Taiwan.

BACKGROUND/PURPOSE: Chronic hepatitis C virus (HCV) infection is a major cause of morbidity and mortality in patients with hemophilia. However, the efficacy and safety of pegylated interferon (PEG-IFN) plus ribavirin (RBV) for hemophilic patients with chronic HCV infection in Taiwan are still unknown. The aim of this study is to report the efficacy and safety of PEG-IFN plus RBV in a single center in Taiwan. METHODS: In an open-label single-treatment one-arm cohort study, 12 hemophilic patients with elevated alanine aminotransferase level more than two times the upper limit of normal for more than 3 months received 180 µg/week of PEG-IFN-α-2a plus RBV 1000-1200 mg/day at a cut-off value of 75 kg. The duration of treatment was 48 weeks for patients with HCV Genotype 1/4 infection and 24 weeks for patients with HCV Genotype 2/3 infection. Efficacy of therapy was expressed as sustained virological response (SVR). RESULTS: Eight patients achieved SVR (66.7%). The SVR rates were 57%, 100%, 100%, and 0% for patients with HCV Genotypes 1, 2, 3, and 4 infection, respectively. Adverse events (AEs) developed in 10 patients (83.3%). Severe thrombocytopenia developed in one patient. However, the patient did not suffer from severe bleeding. CONCLUSION: Our study shows that the SVR rates are similar in hemophilic and nonhemophilic patients with chronic HCV infection who receive PEG-IFN-α-2a plus RBV in Taiwan. The rate of AEs also resembled other studies in nonhemophilic patients in Taiwan. No patient suffered from severe bleeding. However, large-scale, well-conducted studies are still needed to verify the treatment efficacy and safety.

Regular nutrition consultations reduced risk factors for cardiovascular diseases in adults.

OBJECTIVES: This study investigated the effects of regular nutrition consultations on reducing risk factors, including body mass index, body composition, blood pressure, blood lipid profile, blood glucose-related markers, and inflammatory factors for cardiovascular diseases. METHODS: Data were collected from participants (n = 129) who completed eight dietary consultations and were divided into two groups according to the regularity of the consultations: an irregular group (with irregular consultation intervals; n = 39) and a regular group (accepted consultation once every 3 wk; n = 90). RESULTS: Compared with the irregular group, the regular group had more significant reductions in cardiovascular disease risk factors, such as body mass index, body fat, triglycerides, total cholesterol, low-density lipoprotein cholesterol, and insulin levels. Moreover, participants with a body mass index ≥ 27 kg/m2 presented significantly obvious improvements in cardiovascular risk factors, such as body weight; body mass index; visceral fat weight; and triglyceride, total cholesterol, low-density lipoprotein cholesterol, glycated hemoglobin, and insulin levels. CONCLUSION: There is a proven benefit to regular nutrition consultation for adults with risk factors of cardiovascular diseases, particularly those who are obese.

Truncation of GalNAc-type O-glycans Suppresses CD44-mediated Osteoclastogenesis and Bone Metastasis in Breast Cancer.

The glycoprotein CD44 is a key regulator of malignant behaviors in breast cancer cells. To date, hyaluronic acid (HA)-CD44 signaling pathway has been widely documented in the context of metastatic bone diseases. Core 1 ß1,3-galactosyltransferase (C1GALT1) is a critical enzyme responsible for the elongation of O-glycosylation. Aberrant O-glycans is recognized as a hallmark in cancers. However, the effects of C1GALT1 on CD44 signaling and bone metastasis remain unclear. In this study, IHC analysis indicated that C1GALT1 expression positively correlates with CD44 in breast cancer. Silencing C1GALT1 accumulates the Tn antigen on CD44, which decreases CD44 levels and osteoclastogenic signaling. Mutations in the O-glycosites on the stem region of CD44 impair its surface localization as well as suppress cell-HA adhesion and osteoclastogenic effects of breast cancer cells. Furthermore, in vivo experiments demonstrated the inhibitory effect of silencing C1GALT1 on breast cancer bone metastasis and bone loss. In conclusion, our study highlights the importance of O-glycans in promoting CD44-mediated tumorigenic signals and indicates a novel function of C1GALT1 in driving breast cancer bone metastasis. IMPLICATIONS: Truncation of GalNAc-type O-glycans by silencing C1GALT1 suppresses CD44-mediated osteoclastogenesis and bone metastasis in breast cancer. Targeting the O-glycans on CD44 may serve as a potential therapeutic target for blocking cancer bone metastasis.

NKG2A and circulating extracellular vesicles are key regulators of natural killer cell activity in prostate cancer after prostatectomy.

Extracellular vesicles (EVs) are an important regulatory factor for natural killer cell activity (NKA) in the tumor microenvironment. The relationship between circulating EVs in the peripheral blood and natural killer (NK) cells in prostate cancer (PCa) is unclear. This study aimed at investigating the key regulators in the interaction between circulating EVs and NK cells in PCa patients before and after tumor removal. NK-cell characteristics were prospectively assessed in 79 patients treated with robot-assisted laparoscopic radical prostatectomy preoperatively and postoperatively. Compared with healthy donors, the existence of prostate tumors increased the number of circulating EVs and altered ligand expression of EVs. Circulating EVs extracted from cancer patients significantly decreased NKA of NK cells compared with those extracted from healthy donors. Upon treatment with an inhibiting antibody or small interfering RNA, natural killer cell protein group 2A (NKG2A) was identified as the main NKA regulator in cancer patients for accepting the signal from circulating EVs. After surgery, NKA was increased and NKG2A expression on NK cells was significantly reduced. The expression of ligands for natural killer cell protein group 2D (NKG2D) on EVs and the level of circulation EVs both significantly increased. With the decrease in NKG2A levels on NK cells and the increase in total NKG2D ligands on circulating EVs, which was increased postoperatively, both NKG2A on NK cells and NKG2D ligands on circulating exosomes are main regulators of NKA restoration after prostatectomy.

miR-24 up-regulation in oral carcinoma: positive association from clinical and in vitro analysis.

MicroRNAs (miRNAs) play important roles in neoplastic process. miR-24 is localized on chromosome 9q22 and 19p13, regions frequently altered in oral squamous cell carcinoma (OSCC). This study showed that miR-24 was up-regulated in OSCC tissues relative to control samples. In addition, the plasma levels of miR-24 in OSCC patients were significantly higher than in control individuals. miR-24 expression was also higher in OSCC cell lines relative to normal oral keratinocytes. Experiments blocking miR-24 and using exogenous miR-24 expression indicated that miR-24 contributes to the growth of OSCC cells and that miR-24 may target p57. This study suggests that miR-24 is involved in the regulation of OSCC growth and that the miR-24's level in plasma may be validatable as a tumor marker for OSCC patients.