Advances of Wnt/ß-catenin Signaling Pathway in Lung Cancer: A review.

Lung cancer is currently the leading cause of cancer mortality and morbidity worldwide and greatly burdens humanity. Therefore, the prevention and treatment of lung cancer remains a serious global problem. The Wnt/ß-catenin signaling pathway also regulates tumor cell growth and invasion through epithelial-mesenchymal transition and tumor stem cells. In this review, we first summarise the role of the Wnt/ß-catenin signaling pathway in lung cancer, focusing on the reported links in the Wnt/ß-catenin signaling pathway that are relevant to lung cancer cell line growth, cell survival, and patient prognosis. Then describe the advances in the Wnt/ß-catenin signaling pathway in lung cancer therapy, the precise regulation of the Wnt/ß-catenin signaling pathway, that precise regulation of the Wnt/ß-catenin signaling pathway should be used to balance anti-tumor effects and adverse events.

Prognostic Value of Pre-Treatment Neutrophil-To-Lymphocyte Ratio and Platelet-To-Lymphocyte Ratio in Patients With Brain Metastasis From Lung Cancer: A systematic Review and Meta-Analysis.

In modern clinical medicine, lung cancer is one of the most common types of cancer, and the brain is a routine organ of metastasis. Recently, researchers have evaluated hematologic indicators, such as the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), and confirmed that they are valid indices for predicting the outcome of patients with lung cancer. However, their prognostic significance for patients with lung cancer who have progressed to brain metastasis (BM) has not been clarified. Our study performed and reported a meta-analysis focusing on the association of pre-treatment NLR, PLR, and overall survival (OS) in lung cancer patients with BM. We searched the PubMed, Embase, and China National Knowledge Infrastructure databases using the PRISMA strategy. Meta-analyses of OS were performed using random-effects models because of the significant heterogeneity. We included 11 articles to evaluate NLR and PLR in 1,977 eligible patients. The NLR group consisted of 11 studies whose meta-analysis showed that OS was significantly shorter in patients with high NLR than in those with low NLR (pooled HR=1.84 (95% CI: 1.47-2.31). Five studies were included in the PLR group, and the results suggested that OS was significantly shorter in patients with high PLR than in those with low PLR (pooled HR=1.53 (95% CI: 1.07-2.20). Our meta-analysis showed a statistically significant association between NLR, PLR, and OS. Lower pre-treatment NLR and PLR predicted a better OS.

Entecavir plus Biejia-Ruangan compound reduces the risk of hepatocellular carcinoma in Chinese patients with chronic hepatitis B.

BACKGROUND & AIMS: Chronic hepatitis B (CHB) and liver fibrosis are associated with a high risk of hepatocellular carcinoma (HCC) development. We assessed whether entecavir (ETV) plus Biejia-Ruangan compound (BRC), an anti-fibrotic traditional Chinese medicine, can further reduce the risk of HCC in treatment-naïve Chinese patients with CHB and an Ishak fibrosis score of ≥3 points derived from our parent double-blind randomized placebo-controlled trial. METHODS: After a 72-week comparison between ETV+BRC and ETV+placebo treatment, participants were eligible to enter an open-label treatment phase and were followed up every 6 months. The primary [secondary] endpoints were the incidence of HCC [liver-related deaths, non-HCC events, and non-liver-related deaths]. Modified intention-to-treat (mITT), intention-to-treat (ITT), and per-protocol (PP) populations were defined for the time-to-event analysis. RESULTS: A total of 1,000 patients were recruited; the median age was 42.0 years; 69.9% were male and 58.3% were HBeAg positive. In the mITT population, the 7-year cumulative incidence of HCC [liver-related deaths] was 4.7% [0.2%] for ETV+BRC, which was significantly lower than 9.3% [2.2%] for ETV monotherapy (p = 0.008 [p = 0.030]). Notably, ETV+BRC treatment yielded a lower incidence of HCC in those who did not achieve regression of fibrosis at week 72 than ETV monotherapy (p = 0.018). There were no differences in the other 2 secondary endpoints or safety profiles between the groups. Multivariable Cox proportional regression analysis, including the treatment allocation as a parameter, also demonstrated that ETV+BRC treatment was associated with a reduced incidence of HCC. The ITT and PP analyses showed consistent results. CONCLUSIONS: ETV plus BRC combination treatment could further reduce the risk of HCC and liver-related deaths in patients with CHB and advanced fibrosis or cirrhosis, which may have important clinical implications for HCC prevention. LAY SUMMARY: Patients with chronic hepatitis B virus infection are at an increased risk of developing liver cancer (specifically hepatocellular carcinoma [HCC]). While there are effective antiviral treatments that can suppress the virus in chronically infected patients, the risk of HCC remains. Herein, we show that adding a traditional Chinese medicine called Biejia-Ruangan compound to an antiviral reduced the risk of HCC in patients with chronic hepatitis B.

Plumbagin-loaded aptamer-targeted poly D,L-lactic-co-glycolic acid-b-polyethylene glycol nanoparticles for prostate cancer therapy.

Plumbagin inhibits the growth, metastasis, and invasion of prostate cancer (PCa). However, its lower bioavailability limits biopharmaceutical properties due to insolubility in water. Prostate-specific membrane antigen (PSMA) aptamer-targeted nanoparticles (NPs) significantly enhanced cytotoxicity in prostate epithelial cells. This study aimed to investigate the effects of plumbagin-loaded prostate-specific membrane antigen (PSMA) aptamer-targeted poly D,L-lactic-co-glycolic acid-b-polyethylene glycol (PLGA-PEG) nanoparticles (NPs) on prostate cancer (PCa) in vitro.PLGA-PEG with a terminal carboxylic acid group (PLGA-PEG-COOH) was synthesized, and plumbagin was loaded on PLGA-PEG-COOH NPs using the nanoprecipitation method and characterized by field emission scanning electron microscopy (SEM), transmission electron microscopy (TEM), and laser light scattering. The uptake and distribution of plumbagin-NPs in human PCa LNCaP cells were investigated by fluorescent labeling. Subsequently, PSMA antibody-targeted PLGA-PEG-COOH NPs (targeted NPs) were prepared by covalent binding and characterized by x-ray photoelectron spectroscopy. Furthermore, the anticancer activity of plumbagin-loaded, targeted NPs was compared with that of nontargeted NPs in LNCaP cells in vitro.Plumbagin-NPs (diameter of 189.4 ±â€Š30.6 nm and zeta potential of -17.1 ±â€Š3.7 mV) were optimized based on theoretical drug loading of 5% and a ratio of water:acetone of 3:1. During the first 2 hours, the cumulative release rate of the drug was 66.4 ±â€Š8.56%. Moreover, plumbagin-targeted NPs with nitrogen atoms were prepared. The uptake rate was 90% at 0.5 hours for targeted and nontargeted NPs. The IC50 of targeted NPs and nontargeted NPs was 32.59 ±â€Š8.03 µM and 39.02 ±â€Š7.64 µM, respectively.Plumbagin-loaded PSMA aptamer-targeted NPs can be used in targeted chemotherapy against PCa.

Blocking and reversing hepatic fibrosis in patients with chronic hepatitis B treated by traditional Chinese medicine (tablets of biejia ruangan or RGT): study protocol for a randomized controlled trial.

BACKGROUND: Chronic hepatitis B (CHB) can progress to cirrhosis, hepatocellular carcinoma (HCC) and ultimately liver-related death. Although oral antiviral therapy for patients with CHB reduces the risk of such complications, once cirrhosis is established, the benefits of antiviral therapy are not robustly demonstrated. According to traditional Chinese medicine (TCM), some Chinese herbal medicines promote blood circulation and soften hard masses, and therefore they may block and reverse hepatic fibrosis. The aim of this study is to evaluate the effects of TCM tablets of the compound biejia ruangan (RGT) administered for fibrosis, and entecavir (ETV), on the development of HCC in patients with CHB or hepatitis B virus (HBV)-related compensated cirrhosis. METHODS/DESIGN: This multicenter, centrally randomized, double-blind, placebo-controlled, parallel-group study is planned to complete within 5 years. For the study, 1,000 with CHB or HBV-related compensated cirrhosis are randomly assigned in a 1:1 ratio to a treatment group (0.5 mg ETV once daily; 2 g RGT three times daily) or a control group (0.5 mg ETV once daily; 2 g RGT dummy agent three times daily). The primary end points are the development of HCC and liver-related death. Secondary end points include disease progression and overall survival. DISCUSSION: Although antiviral therapy can achieve sustained suppression of HBV replication, thereby preventing cirrhosis, patients with CHB treated with nucleos(t)ide analogs (NUCs) retain a higher risk for HCC compared with patients with inactive disease. Although previous clinical trials with RGT have confirmed the efficacy of blocking and reversing hepatic fibrosis in patients with CHB or compensated cirrhosis, the long-term risk for HCC or disease progression in these patients treated with combination of RGT and NUCs compared with NUCs alone is unclear. Therefore, it is necessary to investigate the effects of the RGT blockade and reversal of hepatic fibrosis on the development of HCC in patients with CHB or HBV-related compensated cirrhosis in large, prospective, multicenter, double-blind, randomized, controlled trials in China. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01965418. Date registered: 17 October 2013.

Ellagitannin (BJA3121), an anti-proliferative natural polyphenol compound, can regulate the expression of MiRNAs in HepG2 cancer cells.

MicroRNAs (miRNAs) play an important role in cancers. A number of miRNA expression-profiling studies have been done to identify the miRNA signatures of cancers from different cellular origin. There is, however, relatively little information on how anticancer agents regulate miRNA expression. Ellagitannin (BJA3121), 1,3-Di-O-galloyl-4,6-(s)-HHDP-b-D-glucopyranose, is a new natural polyphenol compound isolated from Balanophora Japonica MAKINO. Our preliminary results have shown that BJA3121 had antiproliferative effect and modified the expression of different genes in human HepG(2) cancer cells. In this study, we further evaluate whether this antineoplastic compound is able to alter miRNA expression in HepG(2) cells. We demonstrated for the first time that BJA3121 can regulate the expression of 25 miRNAs, including 17 upregulated and 8 downregulated miRNAs in HepG(2) cells. Our results suggested that BJA3121-modifed miRNA expression can mediate, at least in part, the antiproliferative and multigene regulatory action induced by the compound on HepG(2) cancer cells.

Neuronal SH2B1 is essential for controlling energy and glucose homeostasis.

SH2B1 (previously named SH2-B), a cytoplasmic adaptor protein, binds via its Src homology 2 (SH2) domain to a variety of protein tyrosine kinases, including JAK2 and the insulin receptor. SH2B1-deficient mice are obese and diabetic. Here we demonstrated that multiple isoforms of SH2B1 (alpha, beta, gamma, and/or delta) were expressed in numerous tissues, including the brain, hypothalamus, liver, muscle, adipose tissue, heart, and pancreas. Rat SH2B1beta was specifically expressed in neural tissue in SH2B1-transgenic (SH2B1(Tg)) mice. SH2B1(Tg) mice were crossed with SH2B1-knockout (SH2B1(KO)) mice to generate SH2B1(TgKO) mice expressing SH2B1 only in neural tissue but not in other tissues. Systemic deletion of the SH2B1 gene resulted in metabolic disorders in SH2B1(KO) mice, including hyperlipidemia, leptin resistance, hyperphagia, obesity, hyperglycemia, insulin resistance, and glucose intolerance. Neuron-specific restoration of SH2B1beta not only corrected the metabolic disorders in SH2B1(TgKO) mice, but also improved JAK2-mediated leptin signaling and leptin regulation of orexigenic neuropeptide expression in the hypothalamus. Moreover, neuron-specific overexpression of SH2B1 dose-dependently protected against high-fat diet-induced leptin resistance and obesity. These observations suggest that neuronal SH2B1 regulates energy balance, body weight, peripheral insulin sensitivity, and glucose homeostasis at least in part by enhancing hypothalamic leptin sensitivity.

[Purification of small peptide from Agkistrodon blomhoffii Bioe and its inhibition on platelet aggregation].

This is the first report to purify a new peptide SV-PP-1 from Agkistrodon blomhoffii Bioe. SV-PP-1 has molecular weight of 1234.616 Da and can inhibit on platelet aggregation. SV-PP-1 significantly inhibited the ADP-induced platelet aggregation. It has been found up to now that SV-PP-1 is the smallest peptide inhibiting on platelet aggregation from snake venom.

[Purification and characteristics of polypeptide with inhibition of platelet aggregation from Agkistrodon blomhoffii Bioe].

A polypeptide, SV-PP-2, was purified from Agkistrodon blomhoffii Bioe by HPLC C18 column. The SV-PP-2 has molecular weight of 23339.00 Da, and can inhibit the ADP-induced platelet aggregation in dose-dependent manner. There have been no such polypeptides reported yet which has inhibition of platelet aggregation and similar molecular weight to SV-PP-2.