Overexpression of HSP27 and HSP70 is associated with decreased survival among patients with esophageal adenocarcinoma

BACKGROUND Overexpression of heat shock proteins (HSPs) is associated with several malignancies and contributes to the development, progression, and metastasis of cancer, in addition to the inhibition of cellular death. In recent years, there has been active research into using HSP inhibitors in several malignancies. Due to the poor prognosis of esophageal adenocarcinoma (EAC), it would be valuable to find new biomarkers for the development of cancer treatments. AIM To evaluate the expressions of HSP27 and HSP70 and their effect on survival in EAC. METHODS Immunohislochemical analyses and evaluations of HSP27 and HSP70 expression were performed on all available samples from 93 patients diagnosed with EAC between 1990 and 2007 at two university hospitals. Fifteen cases with Barrett's metaplasia and 5 control cases from the same patient population were included in the analysis. HSP expression was quantitatively assessed and classified as high or low. Kaplan-Meier analyses and Cox regression models adjusting for age and sex as well as tumor site, stage, and grade were used to evaluate the effect on survival. RESULTS Tumor stage and surgical treatment were the main prognostic factors. High HSP27 expression in cancer cases was a strong negative predictive factor, with a mean survival of 23 mo compared to the 49 mo in cases with a low expression (P = 0.018). The results were similar for HSP70, with a poorer survival of 17 mo in cases with high HSP70 expression, in contrast to 40 mo (P = 0.006) in cases with a low expression. A Cox regression survival analysis was performed, adjusting for possible confounding factors, and higher HSP27 and HSP70 expressions remained an independent negative prognostic factor. The HSPs' correlation with survival was not affected by cancer treatments. When the analysis was adjusted for all factors, the odds ratios for HSP27 and HSP70 were 3.3 (CI: 1.6-6.6, P = 0.001) and 2.2 (CI: 1.2-3.9, P = 0.02), respectively. CONCLUSION HSP27 and HSP70 overexpression is associated with poor survival in EAC, which is, to the best of our knowledge, reported for the first time.Peer reviewe

Akalasia

Vertaisarvioitu.Akalasia on harvinainen ruokatorven sairaus, joka aiheuttaa ruokatorven alasulkijan relaksaatiohäiriön ja runko-osan motiliteettihäiriön. Nämä johtavat ruuan nielemisvaikeuteen, käänteisvirtaukseen, rintakipuihin ja joskus painon vähenemiseen. Diagnoosiin päästään tarkkuusmanometrialla. Parantavaa hoitoa ei ole, mutta oireita voidaan lievittää löystyttämällä ruokatorven alasulkijaa joko endoskooppisella pallolaajennnuksella tai leikkaamalla sulkijalihas poikki joko laparoskopiassa (Heller-Dorin leikkaus) tai endoskopiassa (peroraalinen endoskooppinen myotomia, POEM). Monisairaiden potilaiden hoidossa voidaan joskus turvautua farmakologisiin hoitokeinoihin eli suun kautta otettaviin nitraatteihin tai kalsiumin estäjiin taikka botuliinitoksiiniruiskeisiin, mutta niiden teho on rajallinen. Pieni osa potilaista päätyy ruokatorviresektioon taudin edettyä.Peer reviewe

Novel stress corrosion testing method for high‐strength steels

Abstract This paper presents a novel TFT (tuning fork test) stress corrosion testing method, which was developed for classifying martensitic high‐strength steels. The novel method was developed by applying finite element calculations to optimize a tuning fork geometry to enable accurate stress adjustment with simple inexpensive equipment. Different steels were exposed to cathodic hydrogen charging conditions with various elastic tensile stress levels that were achieved by displacement control. All steels exhibited hydrogen‐induced stress corrosion cracking after exceeding a material‐specific threshold stress level that decreased linearly with increasing hardness

Hydrogen‐induced stress corrosion cracking studied by the novel tuning‐fork test method

Abstract A novel tuning‐fork test method was developed to study hydrogen‐induced stress corrosion cracking of high‐strength steels. Special tuning‐fork specimens are designed to enable accurate stress adjustment via constant displacement under cathodic hydrogen charging conditions. In this study, the testing method is further developed, making the potentiostatic hydrogen charging possible through the modifications of the corrosion cell. Different direct‐quenched, low‐ and medium‐carbon steel grades, with a hardness range of 300–550 HBW, are investigated with both galvanostatic and potentiostatic hydrogen charging techniques. For each steel grade, the lowest fracture stress and highest no‐fracture stress are determined. Both hydrogen charging techniques produce similar results, and it is observed that the fracture stress decreases with the increase in hardness. However, the potentiostatic technique produces larger differences between the lowest fracture stress results, thus having a better resolution

Genetic architecture of human plasma lipidome and its link to cardiovascular disease

Abstract Understanding genetic architecture of plasma lipidome could provide better insights into lipid metabolism and its link to cardiovascular diseases (CVDs). Here, we perform genome-wide association analyses of 141 lipid species (n = 2,181 individuals), followed by phenome-wide scans with 25 CVD related phenotypes (n = 511,700 individuals). We identify 35 lipid-species-associated loci (P <5 ×10−8), 10 of which associate with CVD risk including five new loci-COL5A1, GLTPD2, SPTLC3, MBOAT7 and GALNT16 (false discovery rate<0.05). We identify loci for lipid species that are shown to predict CVD e.g., SPTLC3 for CER(d18:1/24:1). We show that lipoprotein lipase (LPL) may more efficiently hydrolyze medium length triacylglycerides (TAGs) than others. Polyunsaturated lipids have highest heritability and genetic correlations, suggesting considerable genetic regulation at fatty acids levels. We find low genetic correlations between traditional lipids and lipid species. Our results show that lipidomic profiles capture information beyond traditional lipids and identify genetic variants modifying lipid levels and risk of CVD