Entity

Time filter

Source Type

New Philadelphia, PA, United States

Di Benedetto A.,University of Washington | Watkins M.,University of Washington | Grimston S.,University of Washington | Salazar V.,University of Washington | And 5 more authors.
Journal of Cell Science | Year: 2010

We have previously shown that targeted expression of a dominant-negative truncated form of N-cadherin (Cdh2) delays acquisition of peak bone mass in mice and retards osteoblast differentiation; whereas deletion of cadherin 11 (Cdh11), another osteoblast cadherin, leads to only modest osteopenia. To determine the specific roles of these two cadherins in the adult skeleton, we generated mice with an osteoblast/osteocyte specific Cdh2 ablation (cKO) and double Cdh2+/-;Cdh11-/- germline mutant mice. Age-dependent osteopenia and smaller diaphyses with decreased bone strength characterize cKO bones. By contrast, Cdh2+/-;Cdh11-/- exhibit severely reduced trabecular bone mass, decreased in vivo bone formation rate, smaller diaphyses and impaired bone strength relative to single Cdh11 null mice. The number of bone marrow immature precursors and osteoprogenitor cells is reduced in both cKO and Cdh2+/-;Cdh11-/- mice, suggesting that N-cadherin is involved in maintenance of the stromal cell precursor pool via the osteoblast. Although Cdh11 is dispensable for postnatal skeletal growth, it favors osteogenesis over adipogenesis. Deletion of either cadherin reduces β-catenin abundance and β-catenin-dependent gene expression, whereas N-cadherin loss disrupts cell-cell adhesion more severely than loss of cadherin 11. Thus, Cdh2 and Cdh11 are crucial regulators of postnatal skeletal growth and bone mass maintenance, serving overlapping, yet distinct, functions in the osteogenic lineage. Source


Wang A.,Shanghai Pulmonary Hospital | Wang H.Y.,Central Laboratory | Liu Y.,Shanghai Pulmonary Hospital | Zhao M.C.,Shanghai Pulmonary Hospital | And 6 more authors.
European Journal of Surgical Oncology | Year: 2015

Background: A meta-analysis was conducted to investigate the much-debated relationship between the gene expression of programmed cell death-ligand 1 (PD-L1) and cancer patient prognosis. The prognostic value of measuring PD-L1 expression in non-small cell lung cancer (NSCLC) patients was analyzed. Methods: We searched PubMed for studies about the relationship between PD-L1 expression and NSCLC patient prognosis. Only studies with patient survival data related to PD-L1 expression in NSCLC patients with different characteristics were included. The effect size (ES) for this analysis was the hazard ratio (HR) with 95% confidence intervals (CI) for overall survival (OS). Results: Six studies with 1157 patients were included with the defined including and excluding criteria. There is no significant heterogeneity among the studies (I2 = 0%, p = 0.683). PD-L1 expression was significantly associated with the differentiation of tumor (poor vs. well: OR = 1.91, 95% CI: 1.33-2.75, p = 0.001). High PD-L1 expression was also correlated with poor prognosis in terms of the OS of patients with NSCLC (pooled HR = 1.75, 95% CI: 140-2.20, p < 0.001; heterogeneity test: I2 = 0%, p = 0.643). Conclusions: NSCLC patients with positive PD-L1 expression exhibited poor OS. The PD-L1 expression was higher in tumors with poor differentiation. © 2015 Elsevier Ltd. All rights reserved. Source


Radice G.L.,Center for Translational Medicine
Progress in Molecular Biology and Translational Science | Year: 2013

Of the 20 classical cadherin subtypes identified in mammals, the functions of the two initially identified family members E- (epithelial) and N- (neural) cadherin have been most extensively studied. E- and N-Cadherin have mostly mutually exclusive expression patterns, with E-cadherin expressed primarily in epithelial cells, whereas N-cadherin is found in a variety of cells, including neural, muscle, and mesenchymal cells. N-Cadherin function, in particular, appears to be cell context-dependent, as it can mediate strong cell-cell adhesion in the heart but induces changes in cell behavior in favor of a migratory phenotype in the context of epithelial-mesenchymal transition (EMT). The ability of tumor cells to alter their cadherin expression profile, for example, E- to N-cadherin, is critical for malignant progression. Recent advances in mouse molecular genetics, and specifically tissue-specific knockout and knockin alleles of N-cadherin, have provided some unexpected results. This chapter highlights some of the genetic studies that explored the complex role of N-cadherin in embryonic development and disease. © 2013 Elsevier Inc. Source


Shao Y.,Xian Jiaotong University | Qu Y.,Xian Jiaotong University | Dang S.,Xian Jiaotong University | Yao B.,Xian Jiaotong University | Ji M.,Center for Translational Medicine
Cancer Cell International | Year: 2013

Background: MicroRNAs (miRNAs) are a large group of negative gene regulators that potentially play a critical role in tumorigenesis. Increasing evidences indicate that miR-145 acts a tumor suppressor in numerous human cancers. However, its role in oral carcinogenesis remains poorly defined. The aim of this study is to determine expression levels of miR-145 in oral squamous cell carcinomas (OSCCs) and normal mucosa tissues, and explore its biological functions in OSCCs.Methods: Reverse transcription quantitative real-time PCR (RT-qPCR) assay was used to evaluate expression levels of miR-145. The biological functions of miR-145 were determined by cell proliferation and colony formation, cell cycle and apoptosis, as well as cell invasion assay.Results: MiR-145 was frequently down-regulated in OSCCs compared with normal mucosa tissues. Restoring miR-145 expression in OSCC cells dramatically suppressed cell proliferation and colony formation, and induced G1 phase arrest and cell apoptosis. Importantly, our data showed that miR-145 downregulated the expression of c-Myc and Cdk6, which have previously been identified as two direct targets of miR-145.Conclusions: Our data suggest that miR-145 exerts its tumor suppressor function by targeting c-Myc and Cdk6, leading to the inhibition of OSCC cell growth. MiR-145 rescue may thus be a rational for diagnostic and therapeutic applications in OSCC. © 2013 Shao et al.; licensee BioMed Central Ltd. Source


Pleger S.T.,University of Heidelberg | Brinks H.,University of Bern | Ritterhoff J.,University of Heidelberg | Raake P.,University of Heidelberg | And 4 more authors.
Circulation Research | Year: 2013

Gene therapy, aimed at the correction of key pathologies being out of reach for conventional drugs, bears the potential to alter the treatment of cardiovascular diseases radically and thereby of heart failure. Heart failure gene therapy refers to a therapeutic system of targeted drug delivery to the heart that uses formulations of DNA and RNA, whose products determine the therapeutic classification through their biological actions. Among resident cardiac cells, cardiomyocytes have been the therapeutic target of numerous attempts to regenerate systolic and diastolic performance, to reverse remodeling and restore electric stability and metabolism. Although the concept to intervene directly within the genetic and molecular foundation of cardiac cells is simple and elegant, the path to clinical reality has been arduous because of the challenge on delivery technologies and vectors, expression regulation, and complex mechanisms of action of therapeutic gene products. Nonetheless, since the first demonstration of in vivo gene transfer into myocardium, there have been a series of advancements that have driven the evolution of heart failure gene therapy from an experimental tool to the threshold of becoming a viable clinical option. The objective of this review is to discuss the current state of the art in the field and point out inevitable innovations on which the future evolution of heart failure gene therapy into an effective and safe clinical treatment relies. © 2013 American Heart Association, Inc. Source

Discover hidden collaborations