Comparative Functional Genomics Analysis of NNK Tobacco-Carcinogen Induced Lung Adenocarcinoma Development in Gprc5a-Knockout Mice

Background: Improved understanding of lung cancer development and progression, including insights from studies of animal models, are needed to combat this fatal disease. Previously, we found that mice with a knockout (KO) of G-protein coupled receptor 5A (Gprc5a) develop lung tumors after a long latent period (12 to 24 months). Methodology/Principal Findings: To determine whether a tobacco carcinogen will enhance tumorigenesis in this model, we administered 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) i.p. to 2-months old Gprc5a-KO mice and sacrificed groups (n = 5) of mice at 6, 9, 12, and 18 months later. Compared to control Gprc5a-KO mice, NNK-treated mice developed lung tumors at least 6 months earlier, exhibited 2- to 4-fold increased tumor incidence and multiplicity, and showed a dramatic increase in lesion size. A gene expression signature, NNK-ADC, of differentially expressed genes derived by transcriptome analysis of epithelial cell lines from normal lungs of Gprc5a-KO mice and from NNK-induced adenocarcinoma was highly similar to differential expression patterns observed between normal and tumorigenic human lung cells. The NNK-ADC expression signature also separated both mouse and human adenocarcinomas from adjacent normal lung tissues based on publicly available microarray datasets. A key feature of the signature, up-regulation of Ube2c, Mcm2, and Fen1, was validated in mouse normal lung and adenocarcinoma tissues and cells by immunohistochemistry and western blotting, respectively

Intramyocardial hemorrhage and microvascular obstruction after primary percutaneous coronary intervention

Reperfusion may cause intramyocardial hemorrhage (IMH) by extravasation of erythrocytes through severely damaged endothelial walls. The purpose of the study was to evaluate the clinical significance of IMH in relation to infarct size, microvascular obstruction (MVO) and function in patients after primary percutaneous intervention. Forty-five patients underwent cardiovascular MR imaging (CMR) 1 week and 4 months after primary stenting for a first acute myocardial infarction. T2-weighted spin-echo imaging (T2W) was used to assess infarct related edema and IMH, and delayed enhancement (DE) was used to assess infarct size and MVO. Cine CMR was used to assess left ventricular volumes and function at baseline and at 4 months follow-up. In 22 (49%) patients, IMH was detected as areas of attenuated signal in the core of the high signal intensity region on T2W images. Patients with IMH had larger infarcts, higher left ventricular volumes and lower ejection fraction. Contrast-to-noise ratio (CNR) between hyperintense periphery and the hypo-intense core of the T2W ischemic area correlated to peak CKMB, total infarct size and MVO size. Using univariable analysis, CNR predicted ejection fraction at baseline (β = −0.62, P = 0.003) and follow-up (β = −0.84, P < 0.001). However, after multivariable analysis, baseline ejection fraction and presence of MVO were the only parameters that predicted functional changes at follow-up. IMH was found in the majority of patients with MVO after reperfused myocardial infarction. It was closely related to markers of infarct size, MVO and function, but did not have prognostic significance beyond MVO

Environmental Control of Phase Transition and Polyp Survival of a Massive-Outbreaker Jellyfish

A number of causes have been proposed to account for the occurrence of gelatinous zooplankton (both jellyfish and ctenophore) blooms. Jellyfish species have a complex life history involving a benthic asexual phase (polyp) and a pelagic sexual phase (medusa). Strong environmental control of jellyfish life cycles is suspected, but not fully understood. This study presents a comprehensive analysis on the physicochemical conditions that control the survival and phase transition of Cotylorhiza tuberculata; a scyphozoan that generates large outbreaks in the Mediterranean Sea. Laboratory experiments indicated that the influence of temperature on strobilation and polyp survival was the critical factor controlling the capacity of this species to proliferate. Early life stages were less sensitive to other factors such as salinity variations or the competitive advantage provided by zooxanthellae in a context of coastal eutrophication. Coherently with laboratory results, the presence/absence of outbreaks of this jellyfish in a particular year seems to be driven by temperature. This is the first time the environmental forcing of the mechanism driving the life cycle of a jellyfish has been disentangled via laboratory experimentation. Projecting this understanding to a field population under climatological variability results in a pattern coherent with in situ records

Methylation levels of a novel genetic element, EgNB3 as a candidate biomarker associated with the embryogenic competency of oil palm

The association between DNA methylation status and embryogenic competency in oil palm tissue culture was examined through Representational Difference Analysis (RDA) approach, using methylation-sensitive restriction endonucleases. "Difference Products" (DPs) of RDA derived from palms of similar genetic backgrounds but exhibiting different embryogenesis rates during the regeneration process were isolated. The DPs were sequenced using a pyrosequencing platform. To our knowledge, this is the first study profiling partial HpaII methylation sites in oil palm young leaf tissues which are potentially associated with embryogenic amenability through a genomic subtractive approach. Quantitative real-time PCR analysis demonstrated that the methylation status of a novel fragment, EgNB3, was higher in highly embryogenic leaf explants compared to low embryogenesis rate materials. These differences are likely to be contributed by the 5′-mCCGG-3′ and/or 5′-mCmCGG-3′ methylation patterns. Our data suggest that the differentially methylated site in EgNB3 has potential as a molecular biomarker for the screening of oil palm leaf explants for their embryogenic potentials

GliMR: Cross-Border Collaborations to Promote Advanced MRI Biomarkers for Glioma

Purpose: There is an annual incidence of 50,000 glioma cases in Europe. The optimal treatment strategy is highly personalised, depending on tumour type, grade, spatial localization, and the degree of tissue infiltration. In research settings, advanced magnetic resonance imaging (MRI) has shown great promise as a tool to inform personalised treatment decisions. However, the use of advanced MRI in clinical practice rem

Combined proteome and transcriptome analyses for the discovery of urinary biomarkers for urothelial carcinoma

Background: Proteomic discovery of cancer biomarkers in body fluids is challenging because of their low abundance in a complex background. Altered gene expression in tumours may not reflect protein levels in body fluids. We have tested combining gene expression profiling of tumours with proteomic analysis of cancer cell line secretomes as a strategy to discover urinary biomarkers for bladder cancer. Methods: We used shotgun proteomics to identify proteins secreted by three bladder cancer cell lines. Secreted proteins with high mRNA levels in bladder tumours relative to normal urothelium were assayed by ELISA in urine samples from 642 patients. Results: Midkine and HAI-1 were significantly increased in bladder cancer patients, with the highest levels in invasive disease (area under the receiver operating characteristic curve 0.89 vs non-cancer). The urinary concentration of both proteins was too high to be explained by bladder cancer associated haematuria and most likely arises by direct tumour secretion. Conclusions: This ‘dual-omic’ strategy identified tumour secreted proteins whose urine concentrations are increased significantly by bladder cancer. Combined secretome-transcriptome analysis may be more useful than direct proteomic analysis of body fluids for biomarker discovery in both bladder cancer and other tumour type

Expression of nuclear retinoid receptors in normal, premalignant and malignant gastric tissues determined by in situ hybridization

[[abstract]]Retinoids exhibit multiple functions through interaction with nuclear retinoid receptors and have growth-suppressive activity on gastric cancer cells. To better understand the roles of nuclear retinoid receptors during gastric carcinogenesis, we have used in situ hybridization to investigate expression of retinoic acid receptors (RARs) and retinoid x receptors (RXRs) in premalignant and malignant formalin-fixed paraffin-embedded gastric tissues. Histological sections of eight normal, 17 distal normal and nine gastric cancer tissues were hybridized with non-radioactive RNA probes for subtypes of RAR and RXR. Expression of RARα, RARβ, RARγ, RXRα and RXRβ was found in most cell types in gastric mucosa tissues from normal individuals as well as in distal normal tissues from cancer patients. Expression of RARα and RARβ were found in three and seven cancer tissues, respectively, and levels of RXRα mRNA were significantly decreased in poorly differentiated cancer tissues. Among the five investigated nuclear retinoid receptors, only expression of RARα mRNA was significantly decreased in intestinal metaplasia, dysplasia and cancer tissues when compared to adjacent normal tissues. In conclusion, normal gastric mucosa expressed both RARs and RXRs, which supports the physiological role of retinoic acid on normal gastric mucosa. The decrease in RARα expression in premalignant and malignant gastric tissues suggests a significant role of RARα during gastric carcinogenesis.[[notice]]補正完畢[[incitationindex]]SC

T2-weighted cardiovascular magnetic resonance in acute cardiac disease

Cardiovascular magnetic resonance (CMR) using T2-weighted sequences can visualize myocardial edema. When compared to previous protocols, newer pulse sequences with substantially improved image quality have increased its clinical utility. The assessment of myocardial edema provides useful incremental diagnostic and prognostic information in a variety of clinical settings associated with acute myocardial injury. In patients with acute chest pain, T2-weighted CMR is able to identify acute or recent myocardial ischemic injury and has been employed to distinguish acute coronary syndrome (ACS) from non-ACS as well as acute from chronic myocardial infarction