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Olivia Jerczynski, Nicolas Lacroix-Pépin, Eric Boilard, Ezequiel Calvo, Agathe Bernet, Michel A Fortier, Ida Björkgren, Petra Sipilä, Clémence Belleannée
Dicer1 is an endoribonuclease involved in the biogenesis of functional molecules such as microRNAs (miRNAs) and endogenous small interfering RNAs (endo-siRNAs). These small non-coding RNAs are important regulators of post-transcriptional gene expression and participate in the control of male fertility. With the knowledge that 1) Dicer1-dependent factors are required for proper sperm maturation in the epididymis, and that 2) miRNAs are potent mediators of intercellular communication in most biological systems, we investigated the role of Dicer1-dependent factors produced by the proximal epididymis (initial segment/caput)- including miRNAs- on the regulation of epididymal gene expression in the distal epididymis regions (i...
2016: PloS One
Hannah M Bruce, Phillip D Stricker, Ruta Gupta, Richard R Savdie, Anne-Maree Haynes, Kate L Mahon, Hui-Ming Lin, James G Kench, Lisa G Horvath
BACKGROUND: Positive surgical margins (PSMs) in localized prostate cancer (PC) confer a two- to three-fold increased risk of biochemical relapse (BR). Absent/weak AZGP1 expression and Gleason grade ≥4 at the margin are each independent predictors of BR in patients with PSMs. Our study aimed to determine whether the biomarkers AZGP1 expression and Gleason grade at the site of a PSM are significant independent markers of biochemical and clinical relapse (CR) when modeled together and whether one of these biomarkers may be superior in its capacity to predict outcome...
December 2016: Prostate
James D Brooks, Wei Wei, Jonathan R Pollack, Robert B West, Jun Ho Shin, John B Sunwoo, Sarah J Hawley, Heidi Auman, Lisa F Newcomb, Jeff Simko, Antonio Hurtado-Coll, Dean A Troyer, Peter R Carroll, Martin E Gleave, Daniel W Lin, Peter S Nelson, Ian M Thompson, Lawrence D True, Jesse K McKenney, Ziding Feng, Ladan Fazli
BACKGROUND: Given the uncertainties inherent in clinical measures of prostate cancer aggressiveness, clinically validated tissue biomarkers are needed. We tested whether Alpha-2-Glycoprotein 1, Zinc-Binding (AZGP1) protein levels, measured by immunohistochemistry, and RNA expression, by RNA in situ hybridization (RISH), predict recurrence after radical prostatectomy independent of clinical and pathological parameters. METHODS: AZGP1 IHC and RISH were performed on a large multi-institutional tissue microarray resource including 1,275 men with 5 year median follow-up...
November 2016: Prostate
Ming-Yi Xu, Rong Chen, Jing-Xia Yu, Ting Liu, Ying Qu, Lun-Gen Lu
Zinc-α2-glycoprotein 1 (AZGP1) has been found to play important roles in TGF-β1 induced epithelial-to-mesenchymal transition (EMT). However, the mechanisms of AZGP1 inhibiting EMT and its therapeutic potential remain unknown in hepatocellular carcinoma (HCC). AZGP1, TGF-β1 or ERK2 expressions were examined in liver tissues of HCC patients and rat model. The effect of AZGP1 on EMT and crosstalking of TGFβ1-ERK2 signaling in human hepatic cancer cell was tested in vitro and in vivo. Hepatic expression of AZGP1 was nearly deficient in HCC patients and rats...
May 1, 2016: Cancer Letters
Rakesh Bam, Sharmin Khan, Wen Ling, Shelton S Randal, Xin Li, Bart Barlogie, Ricky Edmondson, Shmuel Yaccoby
BACKGROUND: Human primary myeloma (MM) cells do not survive in culture; current in vitro and in vivo systems for growing these cells are limited to coculture with a specific bone marrow (BM) cell type or growth in an immunodeficient animal model. The purpose of the study is to establish an interactive healthy donor whole BM based culture system capable of maintaining prolonged survival of primary MM cells. This normal BM (NBM) coculture system is different from using autologous BM that is already affected by the disease...
November 6, 2015: BMC Cancer
Christoph Burdelski, Sandra Kleinhans, Martina Kluth, Claudia Hube-Magg, Sarah Minner, Christina Koop, Markus Graefen, Hans Heinzer, Maria Christina Tsourlakis, Waldemar Wilczak, Andreas Marx, Guido Sauter, Corinna Wittmer, Hartwig Huland, Ronald Simon, Thorsten Schlomm, Stefan Steurer
Zinc-alpha 2-glycoprotein (AZGP1) is involved in lipid metabolism and was suggested as a candidate prognostic biomarker in prostate cancer. To evaluate the clinical impact and relationship with key genomic alterations in prostate cancer, AZGP1 expression was analyzed by immunohistochemistry on a tissue microarray containing 11,152 prostate cancers. Data on ERG status and PTEN, 3p13, 5q21 and 6q15 deletions were available from earlier studies. AZGP1 expression was strong in benign prostatic glands but absent in 38...
March 1, 2016: International Journal of Cancer. Journal International du Cancer
Ligong Chang, Peng Wu, Ravichandran Senthilkumar, Xiaoqiang Tian, Hui Liu, Xia Shen, Zijian Tao, Peilin Huang
PURPOSE: Altered cellular metabolism has received increased attention as an important hallmark of cancer. Activation of FASN has been found to be involved in many human tumors. Despite extensive research in FASN function on cancer, the underlying mechanism is not entirely understood yet. METHODS: Cerulenin was used to suppress the FASN expression in human colorectal cancer cell lines (HT29 and LoVo). Expression of PI3K, Akt, p-Akt, mTOR, p-mTOR, FASN, and AZGP1 was measured using western blotting and qPCR...
January 2016: Journal of Cancer Research and Clinical Oncology
Katarina Davalieva, Ivana Maleva Kostovska, Sanja Kiprijanovska, Katerina Markoska, Katerina Kubelka-Sabit, Vanja Filipovski, Sotir Stavridis, Oliver Stankov, Selim Komina, Gordana Petrusevska, Momir Polenakovic
BACKGROUND: The key to a more effective diagnosis, prognosis, and therapeutic management of prostate cancer (PCa) could lie in the direct analysis of cancer tissue. In this study, by comparative proteomics analysis of PCa and benign prostate hyperplasia (BPH) tissues we attempted to elucidate the proteins and regulatory pathways involved in this disease. METHODS: The samples used in this study were fresh surgical tissues with clinically and histologically confirmed PCa (n = 19) and BPH (n = 33)...
October 2015: Prostate
Maéva Langouët, Karine Siquier-Pernet, Sylvia Sanquer, Christine Bole-Feysot, Patrick Nitschke, Nathalie Boddaert, Arnold Munnich, Grazia M S Mancini, Robert Barouki, Jeanne Amiel, Laurence Colleaux
We investigated two siblings, born to consanguineous parents, with neurological features reminiscent of adaptor protein complex 4 (AP4) deficiency, an autosomal recessive neurodevelopmental disorder characterized by neonatal hypotonia that progresses to hypertonia and spasticity, severe intellectual disability speech delay, microcephaly, and growth retardation. Yet, both children also presented with early onset obesity. Whole-exome sequencing identified two homozygous substitutions in two genes 170 kb apart on 7q22...
May 2015: Molecular Genetics & Genomic Medicine
Henrik J Johansson, Betzabe C Sanchez, Jenny Forshed, Olle Stål, Helena Fohlin, Rolf Lewensohn, Per Hall, Jonas Bergh, Janne Lehtiö, Barbro K Linderholm
BACKGROUND: Despite the success of tamoxifen since its introduction, about one-third of patients with estrogen (ER) and/or progesterone receptor (PgR) - positive breast cancer (BC) do not benefit from therapy. Here, we aim to identify molecular mechanisms and protein biomarkers involved in tamoxifen resistance. RESULTS: Using iTRAQ and Immobilized pH gradient-isoelectric focusing (IPG-IEF) mass spectrometry based proteomics we compared tumors from 12 patients with early relapses (<2 years) and 12 responsive to therapy (relapse-free > 7 years)...
2015: Clinical Proteomics
Inga Sörensen-Zender, Sagar Bhayana, Nathan Susnik, Veronique Rolli, Sandor Batkai, Arpita Baisantry, Siamak Bahram, Payel Sen, Beina Teng, Robert Lindner, Mario Schiffer, Thomas Thum, Anette Melk, Hermann Haller, Roland Schmitt
Zinc-α2-glycoprotein (AZGP1) is a secreted protein synthesized by epithelial cells and adipocytes that has roles in lipid metabolism, cell cycling, and cancer progression. Our previous findings in AKI indicated a new role for AZGP1 in the regulation of fibrosis, which is a unifying feature of CKD. Using two models of chronic kidney injury, we now show that mice with genetic AZGP1 deletion develop significantly more kidney fibrosis. This destructive phenotype was rescued by injection of recombinant AZGP1. Exposure of AZGP1-deficient mice to cardiac stress by thoracic aortic constriction revealed that antifibrotic effects were not restricted to the kidney but were cardioprotective...
November 2015: Journal of the American Society of Nephrology: JASN
Bo Kong, Philipp Bruns, Susanne Raulefs, Simon Rieder, Laura Paul, Olivia Prazeresda Costa, Thorsten Buch, Fabian J Theis, Christoph W Michalski, Jörg Kleeff
INTRODUCTION: Surgical site infections (SSI) represent a significant cause of morbidity in abdominal surgery. The objective of this study was to determine the gene expression signature in subcutaneous tissues in relation to SSI. METHODS: To determine differences in gene expression, microarray analysis were performed from bulk tissue mRNA of subcutaneous tissues prospectively collected in 92 patients during open abdominal surgery. 10 patients (11%) developed incisional (superficial and deep) SSI...
February 2015: International Journal of Surgery
Yingming Xue, Fudong Yu, Dongwang Yan, Feifei Cui, Huamei Tang, Xiaoliang Wang, Jian Chen, Huijun Lu, Senlin Zhao, Zhihai Peng
Zinc-α-2-glycoprotein (AZGP1) is a 41-kDa secreted glycoprotein, which has been detected in several malignancies. The diagnostic value of AZGP1 in serum of prostate and breast cancer patients has been reported. Analyzing "The Cancer Genome Atlas" data, we found that in colon cancer AZGP1 gene expression was upregulated at transcriptional level. We hypothesized that AZGP1 could be used as a diagnostic marker of colon cancer. First, we confirmed AZGP1 expression was higher in a set of 28 tumor tissues than in normal colonic mucosa tissues by real-time quantitative PCR and western blot in a Chinese population...
2015: International Journal of Molecular Sciences
Juan Manuel Herrero-Medrano, Hendrik-Jan Megens, Martien A M Groenen, Mirte Bosse, Miguel Pérez-Enciso, Richard P M A Crooijmans
BACKGROUND: A major concern in conservation genetics is to maintain the genetic diversity of populations. Genetic variation in livestock species is threatened by the progressive marginalisation of local breeds in benefit of high-output pigs worldwide. We used high-density SNP and re-sequencing data to assess genetic diversity of local pig breeds from Europe. In addition, we re-sequenced pigs from commercial breeds to identify potential candidate mutations responsible for phenotypic divergence among these groups of breeds...
2014: BMC Genomics
Ligong Chang, Xiaoqiang Tian, Yinghui Lu, Min Jia, Peng Wu, Peilin Huang
AZGP1 is a multifaceted protein associated with lipid mobilization, a process that is regulated by FASN and other metabolic pathways such as mTOR signaling. The active mTOR signaling pathway has been found to be involved in a variety of tumors. However, it remains unclear whether it is involved in the regulation of AZGP1 and FASN. An AZGP1-expressing plasmid was transfected into a human colorectal cancer cell line (LoVo) with a low expression of AZGP1. The expression of AZGP1, FASN, eIF4E, p-mTOR, p-S6,and S6K1 were measured by Western blot analysis, and target genes were detected by RT-PCR...
2014: PloS One
Gianluca Severi, Liesel M FitzGerald, David C Muller, John Pedersen, Anthony Longano, Melissa C Southey, John L Hopper, Dallas R English, Graham G Giles, John Mills
Only a minority of prostate cancers lead to death. Because no tissue biomarkers of aggressiveness other than Gleason score are available at diagnosis, many nonlethal cancers are treated aggressively. We evaluated whether a panel of biomarkers, associated with a range of disease outcomes in previous studies, could predict death from prostate cancer for men with localized disease. Using a case-only design, subjects were identified from three Australian epidemiological studies. Men who had died of their disease, "cases" (N = 83), were matched to "referents" (N = 232), those who had not died of prostate cancer, using incidence density sampling...
October 2014: Cancer Medicine
Mathias Fasshauer, Matthias Blüher, Michael Stumvoll
Gestational diabetes is characterised by glucose intolerance with onset or first recognition during pregnancy. The disease shows facets of the metabolic syndrome including obesity, insulin resistance, and dyslipidaemia. Adipokines are a group of proteins secreted from adipocytes, which are dysregulated in obesity and contribute to metabolic and vascular complications. Recent studies have assessed the role of various adipokines including leptin, adiponectin, tumour necrosis factor α (TNFα), adipocyte fatty acid-binding protein (AFABP), retinol-binding protein 4 (RBP4), resistin, NAMPT, SERPINA12, chemerin, progranulin, FGF-21, TIMP1, LCN2, AZGP1, apelin (APLN), and omentin in gestational diabetes...
June 2014: Lancet Diabetes & Endocrinology
Allyson L Valente, Jennifer L Kane, Darrell L Ellsworth, Craig D Shriver, Rachel E Ellsworth
Breast stroma plays an active role in tumorigenesis, undergoing both phenotypic and molecular changes that facilitate and promote tumor development and growth. The metastatic microenvironment also plays a role in successful colonization; however, genetic changes in these secondary microenvironments are not well described. To improve understanding of molecular changes associated with metastatic colonization, gene expression patterns from lymph node tissues from women with at least one positive, as well as one negative node, were compared...
June 2014: Clinical & Experimental Metastasis
Laura Bazzichi, Ylenia Da Valle, Alessandra Rossi, Camillo Giacomelli, Francesca Sernissi, Gino Giannaccini, Laura Betti, Federica Ciregia, Laura Giusti, Pietro Scarpellini, Liliana Dell'Osso, Donatella Marazziti, Stefano Bombardieri, Antonio Lucacchini
OBJECTIVES: To study the effects of both balneotherapy and mud-bath therapy treatments in patients affected by primary fibromyalgia (FM) using rheumatological, psychiatric, biochemical and proteomic approaches. METHODS: Forty-one FM patients (39 females, 2 males), who fulfilled the American College of Rheumatology criteria received a 2-week thermal therapy programme consisting of therapy once daily for 6 days/week. Twenty-one patients received mud-bath treatment, while the other twenty balneotherapy...
November 2013: Clinical and Experimental Rheumatology
Toshima Z Parris, Anikó Kovács, Luaay Aziz, Shahin Hajizadeh, Szilárd Nemes, May Semaan, Eva Forssell-Aronsson, Per Karlsson, Khalil Helou
The deregulation of key cellular pathways is fundamental for the survival and expansion of neoplastic cells, which in turn can have a detrimental effect on patient outcome. To develop effective individualized cancer therapies, we need to have a better understanding of which cellular pathways are perturbed in a genetically defined subgroup of patients. Here, we validate the prognostic value of a 13-marker signature in independent gene expression microarray datasets (n = 1,141) and immunohistochemistry with full-faced FFPE samples (n = 71)...
April 1, 2014: International Journal of Cancer. Journal International du Cancer
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