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Boisen M.K.,Herlev University Hospital | Dehlendorff C.,Danish Cancer Society | Linnemann D.,Herlev University Hospital | Nielsen B.S.,Bioneer | And 14 more authors.
PLoS ONE | Year: 2014

Purpose: We tested the hypothesis that expression of microRNAs (miRNAs) in cancer tissue can predict effectiveness of bevacizumab added to capecitabine and oxaliplatin (CAPEOX) in patients with metastatic colorectal cancer (mCRC).Experimental Design: Patients with mCRC treated with first line CAPEOX and bevacizumab (CAPEOXBEV): screening (n = 212) and validation (n = 121) cohorts, or CAPEOX alone: control cohort (n = 127), were identified retrospectively and archival primary tumor samples were collected. Expression of 754 miRNAs was analyzed in the screening cohort using polymerase chain reaction (PCR) arrays and expression levels were related to time to disease progression (TTP) and overall survival (OS). Significant miRNAs from the screening study were analyzed in all three cohorts using custom PCR arrays. In situ hybridization (ISH) was done for selected miRNAs.Results: In the screening study, 26 miRNAs were significantly correlated with outcome in multivariate analyses. Twenty-two miRNAs were selected for further study. Higher miR-664-3p expression and lower miR-455-5p expression were predictive of improved outcome in the CAPEOXBEV cohorts and showed a significant interaction with bevacizumab effectiveness. The effects were strongest for OS. Both miRNAs showed high expression in stromal cells. Higher expression of miR-196b-5p and miR-592 predicted improved outcome regardless of bevacizumab treatment, with similar effect estimates in all three cohorts.Conclusions: We have identified potentially predictive miRNAs for bevacizumab effectiveness and additional miRNAs that could be related to chemotherapy effectiveness or prognosis in patients with mCRC. Our findings need further validation in large cohorts, preferably from completed randomized trials. © 2014 Boisen et al.


PubMed | Danish Cancer Society, Bioneer, Roskilde Hospital, Rigshospitalet and 7 more.
Type: Journal Article | Journal: PloS one | Year: 2014

We tested the hypothesis that expression of microRNAs (miRNAs) in cancer tissue can predict effectiveness of bevacizumab added to capecitabine and oxaliplatin (CAPEOX) in patients with metastatic colorectal cancer (mCRC).Patients with mCRC treated with first line CAPEOX and bevacizumab (CAPEOXBEV): screening (n=212) and validation (n=121) cohorts, or CAPEOX alone: control cohort (n=127), were identified retrospectively and archival primary tumor samples were collected. Expression of 754 miRNAs was analyzed in the screening cohort using polymerase chain reaction (PCR) arrays and expression levels were related to time to disease progression (TTP) and overall survival (OS). Significant miRNAs from the screening study were analyzed in all three cohorts using custom PCR arrays. In situ hybridization (ISH) was done for selected miRNAs.In the screening study, 26 miRNAs were significantly correlated with outcome in multivariate analyses. Twenty-two miRNAs were selected for further study. Higher miR-664-3p expression and lower miR-455-5p expression were predictive of improved outcome in the CAPEOXBEV cohorts and showed a significant interaction with bevacizumab effectiveness. The effects were strongest for OS. Both miRNAs showed high expression in stromal cells. Higher expression of miR-196b-5p and miR-592 predicted improved outcome regardless of bevacizumab treatment, with similar effect estimates in all three cohorts.We have identified potentially predictive miRNAs for bevacizumab effectiveness and additional miRNAs that could be related to chemotherapy effectiveness or prognosis in patients with mCRC. Our findings need further validation in large cohorts, preferably from completed randomized trials.


Bork-Jensen J.,Steno Diabetes Center | Bork-Jensen J.,Rigshospitalet | Scheele C.,Copenhagen University | Christophersen D.V.,Steno Diabetes Center | And 19 more authors.
Diabetologia | Year: 2014

Methods: We measured muscle miRNA levels in monozygotic (MZ) twins discordant for type 2 diabetes using arrays. Further investigations of selected miRNAs included target prediction, pathway analysis, silencing in cells and association analyses in a separate cohort of 164 non-diabetic MZ and dizygotic twins. The effects of elevated glucose and insulin levels on miRNA expression were examined, and the effect of low birthweight (LBW) was studied in rats.Aims/hypothesis: We aimed to identify microRNAs (miRNAs) associated with type 2 diabetes and risk of developing the disease in skeletal muscle biopsies from phenotypically well-characterised twins.Conclusions: Type 2 diabetes is associated with non-genetic downregulation of several miRNAs in skeletal muscle including miR-15b and miR-16, potentially targeting insulin signalling. The paradoxical findings in twins with overt diabetes and twins at increased risk of the disease underscore the complexity of the regulation of muscle insulin signalling in glucose homeostasis.Results: We identified 20 miRNAs that were downregulated in MZ twins with diabetes compared with their non-diabetic co-twins. Differences for members of the miR-15 family (miR-15b and miR-16) were the most statistically significant, and these miRNAs were predicted to influence insulin signalling. Indeed, miR-15b and miR-16 levels were associated with levels of key insulin signalling proteins, miR-15b was associated with the insulin receptor in non-diabetic twins and knockdown of miR-15b/miR-16 in myocytes changed the levels of insulin signalling proteins. LBW in twins and undernutrition during pregnancy in rats were, in contrast to overt type 2 diabetes, associated with increased expression of miR-15b and/or miR-16. Elevated glucose and insulin suppressed miR-16 expression in vitro. © 2014, Springer-Verlag Berlin Heidelberg.


This report studies Nucleic Acid Purification Systems in Global market, especially in North America, Europe, China, Japan, Southeast Asia and India, focuses on top manufacturers in global market, with production, price, revenue and market share for each manufacturer, covering  Thermo Fisher Scientific  Promega  IBI Scientific  GE Healthcare  Clontech  Affymetrix,Inc.  Bioneer  G-Biosciences  Tecan  Thmorgan  Roche Diagnostics  Vivantis  RBCBio Science  Analytik Jena  PerkinElmer  Eppendorf  Aurore Bio-med  Allsheng  Bioer Market Segment by Regions, this report splits Global into several key Regions, with production, consumption, revenue, market share and growth rate of Nucleic Acid Purification Systems in these regions, from 2011 to 2021 (forecast), like  North America  Europe  China  Japan  Southeast Asia  India Split by product type, with production, revenue, price, market share and growth rate of each type, can be divided into  Type I  Type II  Type III Split by application, this report focuses on consumption, market share and growth rate of Nucleic Acid Purification Systems in each application, can be divided into  Application 1  Application 2  Application 3 Global Nucleic Acid Purification Systems Market Research Report 2016  1 Nucleic Acid Purification Systems Market Overview  1.1 Product Overview and Scope of Nucleic Acid Purification Systems  1.2 Nucleic Acid Purification Systems Segment by Type  1.2.1 Global Production Market Share of Nucleic Acid Purification Systems by Type in 2015  1.2.2 Type I  1.2.3 Type II  1.2.4 Type III  1.3 Nucleic Acid Purification Systems Segment by Application  1.3.1 Nucleic Acid Purification Systems Consumption Market Share by Application in 2015  1.3.2 Application 1  1.3.3 Application 2  1.3.4 Application 3  1.4 Nucleic Acid Purification Systems Market by Region  1.4.1 North America Status and Prospect (2011-2021)  1.4.2 Europe Status and Prospect (2011-2021)  1.4.3 China Status and Prospect (2011-2021)  1.4.4 Japan Status and Prospect (2011-2021)  1.4.5 Southeast Asia Status and Prospect (2011-2021)  1.4.6 India Status and Prospect (2011-2021)  1.5 Global Market Size (Value) of Nucleic Acid Purification Systems (2011-2021) 7 Global Nucleic Acid Purification Systems Manufacturers Profiles/Analysis  7.1 Thermo Fisher Scientific  7.1.1 Company Basic Information, Manufacturing Base and Its Competitors  7.1.2 Nucleic Acid Purification Systems Product Type, Application and Specification  7.1.2.1 Type I  7.1.2.2 Type II  7.1.3 Thermo Fisher Scientific Nucleic Acid Purification Systems Production, Revenue, Price and Gross Margin (2015 and 2016)  7.1.4 Main Business/Business Overview  7.2 Promega  7.2.1 Company Basic Information, Manufacturing Base and Its Competitors  7.2.2 Nucleic Acid Purification Systems Product Type, Application and Specification  7.2.2.1 Type I  7.2.2.2 Type II  7.2.3 Promega Nucleic Acid Purification Systems Production, Revenue, Price and Gross Margin (2015 and 2016)  7.2.4 Main Business/Business Overview  7.3 IBI Scientific  7.3.1 Company Basic Information, Manufacturing Base and Its Competitors  7.3.2 Nucleic Acid Purification Systems Product Type, Application and Specification  7.3.2.1 Type I  7.3.2.2 Type II  7.3.3 IBI Scientific Nucleic Acid Purification Systems Production, Revenue, Price and Gross Margin (2015 and 2016)  7.3.4 Main Business/Business Overview  7.4 GE Healthcare  7.4.1 Company Basic Information, Manufacturing Base and Its Competitors  7.4.2 Nucleic Acid Purification Systems Product Type, Application and Specification  7.4.2.1 Type I  7.4.2.2 Type II  7.4.3 GE Healthcare Nucleic Acid Purification Systems Production, Revenue, Price and Gross Margin (2015 and 2016)  7.4.4 Main Business/Business Overview  7.5 Clontech  7.5.1 Company Basic Information, Manufacturing Base and Its Competitors  7.5.2 Nucleic Acid Purification Systems Product Type, Application and Specification  7.5.2.1 Type I  7.5.2.2 Type II  7.5.3 Clontech Nucleic Acid Purification Systems Production, Revenue, Price and Gross Margin (2015 and 2016)  7.5.4 Main Business/Business Overview  7.6 Affymetrix,Inc.  7.6.1 Company Basic Information, Manufacturing Base and Its Competitors  7.6.2 Nucleic Acid Purification Systems Product Type, Application and Specification  7.6.2.1 Type I  7.6.2.2 Type II  7.6.3 Affymetrix,Inc. Nucleic Acid Purification Systems Production, Revenue, Price and Gross Margin (2015 and 2016)  7.6.4 Main Business/Business Overview  7.7 Bioneer  7.7.1 Company Basic Information, Manufacturing Base and Its Competitors  7.7.2 Nucleic Acid Purification Systems Product Type, Application and Specification  7.7.2.1 Type I  7.7.2.2 Type II  7.7.3 Bioneer Nucleic Acid Purification Systems Production, Revenue, Price and Gross Margin (2015 and 2016)  7.7.4 Main Business/Business Overview  7.8 G-Biosciences  7.8.1 Company Basic Information, Manufacturing Base and Its Competitors  7.8.2 Nucleic Acid Purification Systems Product Type, Application and Specification  7.8.2.1 Type I  7.8.2.2 Type II  7.8.3 G-Biosciences Nucleic Acid Purification Systems Production, Revenue, Price and Gross Margin (2015 and 2016)  7.8.4 Main Business/Business Overview  7.9 Tecan  7.9.1 Company Basic Information, Manufacturing Base and Its Competitors  7.9.2 Nucleic Acid Purification Systems Product Type, Application and Specification  7.9.2.1 Type I  7.9.2.2 Type II  7.9.3 Tecan Nucleic Acid Purification Systems Production, Revenue, Price and Gross Margin (2015 and 2016)  7.9.4 Main Business/Business Overview  7.10 Thmorgan  7.10.1 Company Basic Information, Manufacturing Base and Its Competitors  7.10.2 Nucleic Acid Purification Systems Product Type, Application and Specification  7.10.2.1 Type I  7.10.2.2 Type II  7.10.3 Thmorgan Nucleic Acid Purification Systems Production, Revenue, Price and Gross Margin (2015 and 2016)  7.10.4 Main Business/Business Overview  7.11 Roche Diagnostics  7.12 Vivantis  7.13 RBCBio Science  7.14 Analytik Jena  7.15 PerkinElmer  7.16 Eppendorf  7.17 Aurore Bio-med  7.18 Allsheng  7.19 Bioer


Jeon M.J.,Seoul National University | Lee Y.,Seoul National University | Ahn S.,Chung - Ang University | Lee C.,Korea Basic Science Institute | And 5 more authors.
Acta Radiologica | Year: 2015

Background: Biopsy remains the current gold-standard for assessing non-alcoholic fatty liver disease (NAFLD). To develop a non-invasive means of assessing the disease, 31P magnetic resonance spectroscopy (31P-MRS) has been explored, but the severe spectral overlaps and low signal-to-noise-ratio in 31P-MRS spectra at clinical field strength are clearly limiting factors. Purpose: To investigate potential advantages of high resolution in vivo 31P-MRS in assessing NAFLD. Material and Methods: The study was conducted at 9.4T in control and carbon tetrachloride (CCl4)-treated rats. Rats were divided according to histopathologic findings into a control group (n=15), a non-alcoholic steatohepatitis group (n=17), and a cirrhosis group (n=12). Data were presented with different reference peaks that are commonly used for peak normalization such as total phosphorous signal, phosphomonoester+phosphodiester (PME+PDE), and nucleotide triphosphate (NTP). Then, multivariate analyses were performed. Results: In all spectra PME and PDE were well resolved into phosphoethanolamine (PE) and phosphocholine (PC), and into glycerophosphorylethanolamine (GPE) and glycerophosphorylcholine (GPC), respectively. Those MRS measures quantifiable only in highly resolved spectra had higher correlations with histology than those conventional MRS measures such as PME, PDE, and NTP. The optimized partial least-squares discriminant analysis (PLS-DA) model correctly classified 79% (22/28) of the rats in the training set and correctly predicted 69% (11/16) of the rats in the test set. Conclusion: PE, PC, GPE, GPC, and nicotinamide adenine dinucleotide phosphate (NADP) that can be separately quantifiable in highly resolved spectra may further improve the potential efficacy of 31P-MRS in the diagnosis of NAFLD. © The Foundation Acta Radiologica 2014.


Atkinson S.M.,Novo Nordisk AS | Atkinson S.M.,Copenhagen University | Bleil J.,Charité - Medical University of Berlin | Maier R.,German Rheumatism Research Center | And 10 more authors.
Arthritis Research and Therapy | Year: 2016

Background: The aims of the present study were to determine the relationship between bone destruction and bone formation in the delayed-type hypersensitivity arthritis (DTHA) model and to evaluate the effect of receptor activator of nuclear factor ΚB ligand (RANKL) blockade on severity of arthritis, bone destruction, and bone formation. Methods: DTHA was induced in C57BL/6 mice. Inflammation, erosive joint damage, and new bone formation were semiquantitatively scored by histology. Osteoclast activity was assessed in vivo, and messenger RNA (mRNA) expression of mediators of bone destruction and bone formation were analyzed by mRNA deep sequencing. Serum concentrations of tartrate-resistant acid phosphatase 5b, carboxy-terminal telopeptide I (CTX-I), matrix metalloproteinase 3 (MMP3), and serum amyloid P component (SAP) were determined by enzyme-linked immunosorbent assay. Anti-RANKL monoclonal antibody treatment was initiated at the time of immunization. Results: Bone destruction (MMP3 serum levels, cathepsin B activity, and RANKL mRNA) peaked at day 3 after arthritis induction, followed by a peak in cartilage destruction and bone erosion on day 5 after arthritis induction. Periarticular bone formation was observed from day 10. Induction of new bone formation indicated by enhanced Runx2, collagen X, osteocalcin, MMP2, MMP9, and MMP13 mRNA expression was observed only between days 8 and 11. Anti-RANKL treatment resulted in a modest reduction in paw and ankle swelling and a reduction of serum levels of SAP, MMP3, and CTX-I. Destruction of the subchondral bone was significantly reduced, while no effect on bone formation was seen. Conclusions: Anti-RANKL treatment prevents joint destruction but does not prevent new bone formation in the DTHA model. Thus, although occurring sequentially during the course of DTHA, bone destruction and bone formation are apparently not linked in this model. © 2016 Atkinson et al.


PubMed | Zealand Pharma, Bioneer, Copenhagen University, German Rheumatism Research Center and 4 more.
Type: | Journal: Arthritis research & therapy | Year: 2016

The aims of the present study were to determine the relationship between bone destruction and bone formation in the delayed-type hypersensitivity arthritis (DTHA) model and to evaluate the effect of receptor activator of nuclear factor B ligand (RANKL) blockade on severity of arthritis, bone destruction, and bone formation.DTHA was induced in C57BL/6 mice. Inflammation, erosive joint damage, and new bone formation were semiquantitatively scored by histology. Osteoclast activity was assessed in vivo, and messenger RNA (mRNA) expression of mediators of bone destruction and bone formation were analyzed by mRNA deep sequencing. Serum concentrations of tartrate-resistant acid phosphatase 5b, carboxy-terminal telopeptide I (CTX-I), matrix metalloproteinase 3 (MMP3), and serum amyloid P component (SAP) were determined by enzyme-linked immunosorbent assay. Anti-RANKL monoclonal antibody treatment was initiated at the time of immunization.Bone destruction (MMP3 serum levels, cathepsin B activity, and RANKL mRNA) peaked at day 3 after arthritis induction, followed by a peak in cartilage destruction and bone erosion on day 5 after arthritis induction. Periarticular bone formation was observed from day 10. Induction of new bone formation indicated by enhanced Runx2, collagen X, osteocalcin, MMP2, MMP9, and MMP13 mRNA expression was observed only between days 8 and 11. Anti-RANKL treatment resulted in a modest reduction in paw and ankle swelling and a reduction of serum levels of SAP, MMP3, and CTX-I. Destruction of the subchondral bone was significantly reduced, while no effect on bone formation was seen.Anti-RANKL treatment prevents joint destruction but does not prevent new bone formation in the DTHA model. Thus, although occurring sequentially during the course of DTHA, bone destruction and bone formation are apparently not linked in this model.


PubMed | Bioneer, Seoul National University, Gachon University, Seoul National University of Science and Technology and 2 more.
Type: Journal Article | Journal: Acta radiologica (Stockholm, Sweden : 1987) | Year: 2015

Biopsy remains the current gold-standard for assessing non-alcoholic fatty liver disease (NAFLD). To develop a non-invasive means of assessing the disease, 31P magnetic resonance spectroscopy (31P-MRS) has been explored, but the severe spectral overlaps and low signal-to-noise-ratio in 31P-MRS spectra at clinical field strength are clearly limiting factors.To investigate potential advantages of high resolution invivo 31P-MRS in assessing NAFLD.The study was conducted at 9.4T in control and carbon tetrachloride (CCl4)-treated rats. Rats were divided according to histopathologic findings into a control group (n=15), a non-alcoholic steatohepatitis group (n=17), and a cirrhosis group (n=12). Data were presented with different reference peaks that are commonly used for peak normalization such as total phosphorous signal, phosphomonoester+phosphodiester (PME+PDE), and nucleotide triphosphate (NTP). Then, multivariate analyses were performed.In all spectra PME and PDE were well resolved into phosphoethanolamine (PE) and phosphocholine (PC), and into glycerophosphorylethanolamine (GPE) and glycerophosphorylcholine (GPC), respectively. Those MRS measures quantifiable only in highly resolved spectra had higher correlations with histology than those conventional MRS measures such as PME, PDE, and NTP. The optimized partial least-squares discriminant analysis (PLS-DA) model correctly classified 79% (22/28) of the rats in the training set and correctly predicted 69% (11/16) of the rats in the test set.PE, PC, GPE, GPC, and nicotinamide adenine dinucleotide phosphate (NADP) that can be separately quantifiable in highly resolved spectra may further improve the potential efficacy of 31P-MRS in the diagnosis of NAFLD.

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