Decreased expression of 17β-hydroxysteroid dehydrogenase type 1 is associated with DNA hypermethylation in colorectal cancer located in the proximal colon

<p>Abstract</p> <p>Background</p> <p>The importance of 17β-estradiol (E2) in the prevention of large bowel tumorigenesis has been shown in many epidemiological studies. Extragonadal E2 may form by the aromatase pathway from androstenedione or the sulfatase pathway from estrone (E1) sulfate followed by E1 reduction to E2 by 17-β-hydroxysteroid dehydrogenase (HSD17B1), so <it>HSD17B1 </it>gene expression may play an important role in the production of E2 in peripheral tissue, including the colon.</p> <p>Methods</p> <p><it>HSD17B1 </it>expression was analyzed in colorectal cancer cell lines (HT29, SW707) and primary colonic adenocarcinoma tissues collected from fifty two patients who underwent radical colon surgical resection. Histopathologically unchanged colonic mucosa located at least 10-20 cm away from the cancerous lesions was obtained from the same patients. Expression level of <it>HSD17B1 </it>using quantitative PCR and western blot were evaluated. DNA methylation level in the 5' flanking region of <it>HSD17B1 </it>CpG rich region was assessed using bisulfite DNA sequencing and HRM analysis. The influence of DNA methylation on HSD17B1 expression was further evaluated by ChIP analysis in HT29 and SW707 cell lines. The conversion of estrone (E1) in to E2 was determined by electrochemiluminescence method.</p> <p>Results</p> <p>We found a significant decrease in HSD17B1 transcript (<it>p </it>= 0.0016) and protein (<it>p </it>= 0.0028) levels in colorectal cancer (CRC) from the proximal but not distal colon and rectum. This reduced <it>HSD17B1 </it>expression was associated with significantly increased DNA methylation (<it>p </it>= 0.003) in the CpG rich region located in the 5' flanking sequence of the <it>HSD17B1 </it>gene in CRC in the proximal but not distal colon and rectum. We also showed that 5-dAzaC induced demethylation of the 5' flanking region of <it>HSD17B1</it>, leading to increased occupation of the promoter by Polymerase II, and increased transcript and protein levels in HT29 and SW707 CRC cells, which contributed to the increase in E2 formation.</p> <p>Conclusions</p> <p>Our results showed that reduced <it>HSD17B1 </it>expression can be associated with DNA methylation in the 5' flanking region of <it>HSD17B1 </it>in CRC from the proximal colon.</p

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s=7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb(-1) of root s = 7 TeV proton-proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results. (C) 2012 CERN. Published by Elsevier B.V. All rights reserved

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s=7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb-1 of sqrt(s) = 7 TeV proton-proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results

Evidence for a nuclear hexadecapole interaction in the hyperfine spectrum of LiI

The molecular beam electric resonance technique has been used to examine the hyperfine spectrum of 7LiI to determine the nuclear hexadecapole interaction of the iodine nucleus. The nuclear magnetic octupole interaction was also considered but found to be marginally significant. A total of 172 transitions in vibrational states 0-3 and rotational states 1-6 have been included in a fit to determine the iodine nuclear quadrupole, spin-rotation, and hexadecapole interactions, the lithium quadrupole and spin-rotation interactions, and the tensor and scalar parts of the spin-spin interaction. Vibration and rotation dependencies of these constants have been determined

Carbon dioxide fluxes in soil profiles as affected by maize phenology and nitrogen fertilization in the semiarid Loess Plateau

To better understand the responses of subsoil CO2 to maize (Zea mays L) phenology and N fertilization, a field experiment was conducted from 2014 to 2015 in the Changwu Agri-Ecological Station, Shaanxi, China. The experiment included four treatments: unplanted and N-unfertilized soil (CO), unplanted soil amended with 225 kg N ha(-1) (CN), maize planted and N-unfertilized soil (PO), and maize planted soil fertilized with 225 kg N ha(-1) (PN). Soil CO2 concentration at 0-50 cm soil depth, at a resolution of 10 cm, was measured, and the CO2 effluxes were calculated using the gradient method. Soil CO2 concentrations and fluxes in the planted treatments corresponded with maize growth; they rapidly increased from the jointing stage, peaked around the milk stage, and then slowly decreased with plant maturity. CO2 concentrations and fluxes in the planted soil were significantly higher compared to those in the unplanted soil. N inputs significantly decreased (P 0.05) decreased with N inputs in both years. The contributions of the plant-derived CO2 effluxes to the total CO2 effluxes of the 0-50 cm soil layers were affected by maize growth, with two year mean values of 0.49 for the PO treatment and 0.55 for the PN treatment, respectively. The results indicated that subsoil CO2 fluxes were affected by maize phenology and that application of N fertilizer enhanced subsoil CO2 effluxes mainly by increasing plant derived CO2 effluxes during the late growing season. (C) 2016 Elsevier B.V. All rights reserved

A 10-miRNA risk score-based prediction model for pathological complete response to neoadjuvant chemotherapy in hormone receptor-positive breast cancer

Patients with hormone receptor (HR)-positive tumors breast cancer usually experience a relatively low pathological complete response (pCR) to neoadjuvant chemotherapy (NAC). Here, we derived a 10-microRNA risk score (10-miRNA RS)-based model with better performance in the prediction of pCR and validated its relation with the disease-free survival (DFS) in 755 HR-positive breast cancer patients (273, 265, and 217 in the training, internal, and external validation sets, respectively). This model, presented as a nomogram, included four parameters: the 10-miRNA RS found in our previous study, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) status, and volume transfer constant (K-trans). Favorable calibration and discrimination of 10-miRNA RS-based model with areas under the curve (AUC) of 0.865, 0.811, and 0.804 were shown in the training, internal, and external validation sets, respectively. Patients who have higher nomogram score (&gt;92.2) with NAC treatment would have longer DFS (hazard ratio=0.57; 95%CI: 0.39-0.83; P=0.004). In summary, our data showed the 10-miRNA RS-based model could precisely identify more patients who can attain pCR to NAC, which may help clinicians formulate the personalized initial treatment strategy and consequently achieves better clinical prognosis for patients with HR-positive breast cancer