BMP2 promotes lung adenocarcinoma metastasis through BMP receptor 2-mediated SMAD1/5 activation.

Bone morphogenetic protein 2 (BMP2) is highly overexpressed in human non-small cell lung cancer (NSCLC) and correlates with tumor stage and metastatic burden. Although several lines of evidence suggest that BMP2 promotes cell migration and invasiveness in vitro, the in vivo role of BMP2 in the metastasis of lung adenocarcinoma cells remains less well understood. Here, we revealed that BMP2 is highly overexpressed in lung adenocarcinoma patients with lymph node metastasis compared with patients without lymph node metastasis. Using an in vivo orthotopic mouse model, we clearly demonstrated that BMP2 promotes lung adenocarcinoma metastasis. The depletion of BMP2 or its receptor BMPR2 significantly reduced cell migration and invasiveness. We further identified that BMP2/BMPR2-mediated cell migration involves the activation of the SMAD1/5/8 signaling pathway, independent of the KRAS signaling pathway. Significantly, the depletion of SMAD1/5/8 or the inhibition of SMAD1/5/8 by LDN193189 inhibitor significantly reduced cell migration. These findings show that BMP2 promotes NSCLC metastasis, indicating that targeting the BMP2 signaling pathway may represent a potential therapeutic strategy for treating patients with metastatic NSCLC.

Ultrasensitive detection of circulating tumour DNA via deep methylation sequencing aided by machine learning.

The low abundance of circulating tumour DNA (ctDNA) in plasma samples makes the analysis of ctDNA biomarkers for the detection or monitoring of early-stage cancers challenging. Here we show that deep methylation sequencing aided by a machine-learning classifier of methylation patterns enables the detection of tumour-derived signals at dilution factors as low as 1 in 10,000. For a total of 308 patients with surgery-resectable lung cancer and 261 age- and sex-matched non-cancer control individuals recruited from two hospitals, the assay detected 52-81% of the patients at disease stages IA to III with a specificity of 96% (95% confidence interval (CI) 93-98%). In a subgroup of 115 individuals, the assay identified, at 100% specificity (95% CI 91-100%), nearly twice as many patients with cancer as those identified by ultradeep mutation sequencing analysis. The low amounts of ctDNA permitted by machine-learning-aided deep methylation sequencing could provide advantages in cancer screening and the assessment of treatment efficacy.

Temperature effects on the magnetic properties of silicon-steel sheets using standardized toroidal frame.

This study designed a detachable and standardized toroidal test frame to measure the electromagnetic characteristic of toroidal laminated silicon steel specimens. The purpose of the design was to provide the measurements with standardized and controlled environment. The device also can withstand high temperatures (25-300°C) for short time period to allow high temperature tests. The accompanying driving circuit facilitates testing for high frequency (50-5,000 Hz) and high magnetic flux (0.2-1.8 T) conditions and produces both sinusoidal and nonsinusoidal test waveforms. The thickness of the stacked laminated silicon-steel sheets must be 30~31 mm, with an internal diameter of 72 mm and an outer diameter of 90 mm. With the standardized setup, it is possible to carry out tests for toroidal specimen in high temperature and high flux operation. The test results show that there is a tendency of increased iron loss under high temperature operation. The test results with various driving waveforms also provide references to the required consideration in engineering designs.

Cardiac troponin I and creatine kinase isoenzyme MB in patients with intradialytic hypotension.

BACKGROUND: Intradialytic hypotension (IH) has been long recognized as a common complication during hemodialysis (HD) therapy, but few studies have discussed IH-related myocardial injuries and the long-term prognosis of patients prone to IH (HP). METHODS: We conducted a prospective study on 70 chronic HD patients who had no recent occurrences of acute coronary artery syndrome. The patients were divided into two groups: HP (n = 29) and IH resistant (n = 41). While they underwent HD therapy, we monitored and evaluated their baseline data and their patterns of cardiac troponin I (cTnI), creatine kinase, and creatine kinase isoenzyme MB. RESULTS: The HP and IH-resistant patients had similar baseline cardiac marker levels that did not seem to be influenced by uneventful HD therapy. However, if during HD therapy the patients experienced an episode of symptomatic IH, they were found to have significant increases in the creatine kinase MB activity at the end of HD therapy and in the cTnI levels 44 h following HD. After 12 months, the HP patients with baseline cTnI levels > or =0.20 ng/ml were more likely to experience cardiovascular events or death (adjusted odds ratio 15.0, p = 0.012). CONCLUSIONS: Our study showed that, after symptomatic IH episodes, the HP patients were more likely to suffer occult myocardial injuries. HP patients who have high cTnI levels should be closely monitored for cardiovascular diseases.

Long-term clinical follow-up after successful direct coronary stenting without predilatation.

BACKGROUND: Direct stent implantation without predilatation is considered a promising new technique that may reduce procedural time, radiation exposure, ischemic time and cost, but little information is available concerning the long-term outcome. The aim of this study was to investigate the long-term clinical outcome of successful direct stenting without predilatation. METHODS: We prospectively undertook a clinical follow-up program (minimum 8 months) in a consecutive series of 101 patients (113 lesions) who were successfully treated with direct stenting without predilatation. RESULTS: Clinical follow-up was obtained in all 101 patients at a mean period of 12.8 months (range 8 to 18.9). Stress test results were available in 94 patients (94%). During the follow-up period, 23 patients (23%) had one or more events, which included death in 2 patients (2%), target vessel revascularization in 14 (14%), myocardial infarction in 1 (1%) and positive stress test results or recurrence of symptoms (Canadian Cardiovascular Society I to II) treated medically in 6 (6%). Cumulative event-free survival at 8 and 18 months were 80% and 72%, respectively. Long-term clinical event rate was not significantly different among the clinical presentations, lesion types, or stent types. Angiographic follow-up was performed in 43 (43%) patients with 45 lesions. Restenosis (defined as 50% diameter stenosis) was observed in 14 of the lesions (31%). CONCLUSIONS: Direct stenting without predilatation is an effective method of coronary intervention in terms of low long-term clinical event rate.