Identification of alpha-enolase as an autoantigen in lung cancer: Its overexpression is associated with clinical outcomes

Purpose: Although existence of humoral immunity has been previously shown in malignant pleural effusions, only a limited number of immunogenic tumor-associated antigens (TAA) have been identified and associated with lung cancer. In this study, we intended to identify more TAAs in pleural effusion-derived tumor cells. Experimental Design: Using morphologically normal lung tissues as a control lysate in Western blotting analyses, 54 tumor samples were screened with autologous effusion antibodies. Biochemical purification and mass spectrometric identification of TAAs were done using established effusion tumor cell lines as antigen sources. We identified a p48 antigen as of-enolase (ENO1). Semiquantitative immunohistochemistry was used to evaluate expression status of ENO1 in the tissue samples of 80 patients with non-small cell lung cancer (NSCLC) and then correlated with clinical variables. Results: Using ENO1-specifc antiserum, up-regulation of ENO1 expression in effusion tumor cells from 11 of 17 patients was clearly observed compared with human normal lung primary epithelial and non-cancer-associated effusion cells. Immunohistochemical studies consistently showed high level of ENO1 expression in all the tumors we have examined thus far. Log-rank and Cox's analyses of ENO1 expression status revealed that its expression level in primary tumors was a key factor contributing to overall- and progression-free survivals of patients (P < 0.05). The same result was also obtained in the early stage of NSCLC patients, showing that tumors expressing relatively higher ENO1 level were tightly correlated with poorer survival outcomes. Conclusions: Our data strongly support a prognostic role of ENO1 in determining tumor malignancy of patients with NSCLC

Transcriptional regulation of the AP-1 and Nrf2 target gene sulfiredoxin

“Two-cysteine” peroxiredoxins are antioxidant enzymes that exert a cytoprotective effect in many models of oxidative stress. However, under highly oxidizing conditions they can be inactivated through hyperoxidation of their peroxidatic active site cysteine residue. Sulfiredoxin can reverse this hyperoxidation, thus, reactivating peroxiredoxins. Here we review recent investigations that have shed further light on sulfiredoxin’s role and regulation. Studies have revealed sulfiredoxin to be a dynamically regulated gene whose transcription is induced by a variety of signals and stimuli. Sulfiredoxin expression is regulated by the transcription factor AP-1, which mediates its up-regulation by synaptic activity in neurons, resulting in protection against oxidative stress. Furthermore, sulfiredoxin has been identified as a new member of the family of genes regulated by Nuclear factor erythroid 2-related factor (Nrf2) via a conserved cis-acting antioxidant response element (ARE). As such, sulfiredoxin is likely to contribute to the net antioxidative effect of small molecule activators of Nrf2. As discussed here. the proximal AP-1 site of the sulfiredoxin promoter is embedded within the ARE, as is common with Nrf2 target genes. Other recent studies have shown that sulfiredoxin induction via Nrf2 may form an important part of the protective response to oxidative stress in the lung, preventing peroxiredoxin hyperoxidation and, in certain cases, subsequent degradation. We illustrate here that sulfiredoxin can be rapidly induced in vivo by administration of CDDO-TFEA, a synthetic triterpenoid inducer of endogenous Nrf2, which may offer a way of reversing peroxiredoxin hyperoxidation in vivo following chronic or acute oxidative stress

Competition between magnetism and superconductivity in the Y1-xRExPd5B3C0.4 (RE = Er, Ho, By, Gd) systems

We have measured the magnetic and superconducting properties of the intermetallic compounds Y1-xRExPd5B3C0.4 (RE = Er, Ho, Dy, Gd; 0 less than or equal to x less than or equal to 1.0) over wide temperature and magnetic field ranges. The magnetic pair breaking effect is the major mechanism causing the reduction of the T-c. The small value of the Curie-Weiss temperature suggests the coupling between the conduction electrons and the magnetic moment is not strong. The anomalous resistivity in the superconducting state is considered to be due to the occurrence of the long range magnetic ordering of the RE+3 moments. The inter-site interaction between RE3+ local moments is attributed to the Ruderman-Kittel-Kasuya-Yosida indirect exchange interaction via conduction electrons

Upper critical field of borocarbide superconductors

We have investigated the upper critical fields of Y1-xErxNi2B2C and Y1-xErxPd5B3C0.4 (0 less than or equal to x less than or equal to 1) systems by the scaling analysis of the thermal fluctuation conductivity, The experiments were done over wide magnetic field range. We are going to test the thermal fluctuation theory in the borocarbide superconducting systems. According to the scaling analysis, the thermal fluctuation conductivity should be scaled as sigma (f) = (T-2/H)(1/3) F[AT-T-c(H)/(TH)(2/3)]. Because the scaling function is field independent, all scaling curves obtained under various applied fields should converge to a universal curve if the function of T,(H) is properly chosen. We therefore obtain H-c2(T) determined by optimizing the scaling fit, The superconducting coherence length and Ginzburg-Landau parameter kappa in those superconductors are also estimated. We categorize the Y1-xErxNi2B2C and Y1-xErxPd5B3C0.4 systems as strong type-II superconductors

Competition between magnetism and superconductivity in the Y1-xRExPd5B3C0.4 (RE = Er, Ho, By, Gd) systems

We have measured the magnetic and superconducting properties of the intermetallic compounds Y1-xRExPd5B3C0.4 (RE = Er, Ho, Dy, Gd; 0 less than or equal to x less than or equal to 1.0) over wide temperature and magnetic field ranges. The magnetic pair breaking effect is the major mechanism causing the reduction of the T-c. The small value of the Curie-Weiss temperature suggests the coupling between the conduction electrons and the magnetic moment is not strong. The anomalous resistivity in the superconducting state is considered to be due to the occurrence of the long range magnetic ordering of the RE+3 moments. The inter-site interaction between RE3+ local moments is attributed to the Ruderman-Kittel-Kasuya-Yosida indirect exchange interaction via conduction electrons

Disturbance of circadian gene expression in endometrial cancer: Detection by real-time quantitative RT-PCR

Circadian genes control the daily changes of the circadian rhythms in a variety of physiological processes, which in turn regulate many functions in the human body. Disruption of circadian rhythms can have a profound influence on our well-being. We established a set of PCR primers and fluorescent probes to analyze the mRNA levels of nine different circadian genes, and used immunohistochemical methods to study four important circadian proteins in 35 endometrial cancers and their paired non-cancerous tissues. Of these, 13 cases showed reduced expression in all nine circadian genes in the cancerous tissues relative to the paired non-cancerous tissues; the remaining cases showed similar reduced expression in 4-8 of the genes analyzed. Conversely, 3 non-cancerous tissues showed reduced expression in all nine circadian genes in comparison with their respective adjacent cancerous tissues, whereas 6 other non-cancerous tissues showed reduced expression in 6-8 of the circadian genes. These results were also confirmed by immunohistochemical study. Expression of the circadian genes is perturbed in endometrial cancer. Based on these results, we suggest that different circadian rhythms occur in endometrial cancer and non-cancerous tissues. Our results may provide the molecular basis for chronotherapy of endometrial cancer

Somatic mutations of PPP2R1A in ovarian and uterine carcinomas

Exome sequencing of ovarian clear-cell carcinoma has identified somatic mutations in PPP2R1A, a subunit of protein phosphatase 2A. The present study was performed to determine the frequency of PPP2R1A mutations in exon 5, which harbors previously reported mutation hot spots, and adjacent exon 6, in 209 ovarian and 56 uterine tumors of various histologic subtypes. PPP2R1A mutations were demonstrated in 10 of 110 type I ovarian tumors (9.1%) including low-grade serous, low-grade endometrioid, clear-cell, and mucinous carcinomas. In contrast, none of 71 type II ovarian (highgrade serous) carcinomas exhibited PPP2R1A mutations. Moreover, PPP2R1A mutations were observed in 2 of 30 type I uterine (endometrioid) carcinomas (6.7%) and 5 of 26 type II uterine (serous) carcinomas (19.2%). Of the 18 mutations, 13 affected the R182 or 183, and there were 5 novel mutations including 3 involving S256, 1 involving W257, and 1 involving P179. All mutations were located in the \u3b1-helix repeats near the interface between the A subunit and the regulatory B subunit of the enzyme complex. These data provide new evidence that PPP2R1A somatic mutations occur in certain types of uterine and ovarian neoplastic lesions, especially uterine serous carcinomas, and suggest that mutation of PPP2R1A may participate in the pathogenesis of ovarian type I and uterine type II carcinomas

Experimental treatment of bilateral fetal chylothorax using in-utero pleurodesis

Objective To assess the use and efficacy of in-utero pleurodesis for experimental treatment of bilateral fetal chylothorax. Methods This was a study of 78 fetuses with bilateral pleural effusion referred to three tertiary referral centers in Taiwan between 2005 and 2009. Fetuses were karyotyped following amniocentesis and the lymphocyte ratio in the pleural effusion was determined following thoracocentesis. Forty-nine (62.8%) fetuses had a normal karyotype and were recognized to have fetal chylothorax; of these, 45 underwent intrapleural injection of 0.1KE OK-432 per side per treatment. We evaluated clinical (hydrops vs. no hydrops) and genetic (mutations in the reported lymphedema-associated loci: VEGFR3, PTPN11, FOXC2, ITGA9) parameters, as well as treatment outcome. Long-term survival was defined as survival to 1 year of age. Results The overall long-term survival rate (LSR) was 35.6% (16/45); the LSR for non-hydropic fetuses was 66.7% (12/18) and for hydropic fetuses it was 14.8% (4/27). If we included only fetuses with onset of the condition in the second trimester, excluding those with onset in the third trimester, the LSR decreased to 29.4% (10/34). Notably, 29.6% (8/27) of hydropic fetuses had mutations in three of the four loci examined. Conclusions OK-432 pleurodesis appeared to be an experimental alternative to the gold-standard technique of thoracoamniotic shunting in non-hydropic fetal chylothorax. In hydropic fetuses, pleurodesis appeared less effective. Copyright (C) 2011 ISUOG. Published by John Wiley & Sons, Ltd