Institution
French Institute of Health and Medical Research
Government•Paris, France•
About: French Institute of Health and Medical Research is a government organization based out in Paris, France. It is known for research contribution in the topics: Population & Receptor. The organization has 109367 authors who have published 174236 publications receiving 8365503 citations.
Topics: Population, Receptor, Gene, Immune system, Antigen
Papers published on a yearly basis
Papers
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TL;DR: It is shown, using a mouse model of liver cancer, that miR-221 overexpression stimulates growth of tumorigenic murine hepatic progenitor cells, and DNA damage-inducible transcript 4 (DDIT4), a modulator of mTOR pathway, is identified as a bona fide target of miR -221.
Abstract: MicroRNA (miRNAs) are negative regulators of gene expression and can function as tumor suppressors or oncogenes. Expression patterns of miRNAs and their role in the pathogenesis of hepatocellular carcinoma (HCC) are still poorly understood. We profiled miRNA expression in tissue samples (104 HCC, 90 adjacent cirrhotic livers, 21 normal livers) as well as in 35 HCC cell lines. A set of 12 miRNAs (including miR-21, miR-221/222, miR-34a, miR-519a, miR-93, miR-96, and let-7c) was linked to disease progression from normal liver through cirrhosis to full-blown HCC. miR-221/222, the most up-regulated miRNAs in tumor samples, are shown to target the CDK inhibitor p27 and to enhance cell growth in vitro. Conversely, these activities can be efficiently inhibited by an antagomiR specific for miR-221. In addition, we show, using a mouse model of liver cancer, that miR-221 overexpression stimulates growth of tumorigenic murine hepatic progenitor cells. Finally, we identified DNA damage-inducible transcript 4 (DDIT4), a modulator of mTOR pathway, as a bona fide target of miR-221. Taken together, these data reveal an important contribution for miR-221 in hepatocarcinogenesis and suggest a role for DDIT4 dysregulation in this process. Thus, the use of synthetic inhibitors of miR-221 may prove to be a promising approach to liver cancer treatment.
717 citations
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TL;DR: A broader immunological interpretation of these three concepts--immune contexture, Immunoscore, and immunologic constant of rejection--that segregates oncogenic processes independently of their tissue origin is proposed.
716 citations
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TL;DR: The jackknife and the bootstrap are two non parametric methods which provide estimates- of the bias and the variance of an estimator, without any assumption about its statistical distribution.
Abstract: The jackknife and the bootstrap are two non parametric methods which provide estimates- of the bias and the variance of an estimator, without any assumption about its statistical distribution. The jackknife is based on the observation of the estimator for subsamples, generally of size n-1, obtained from the original sample. The bootstrap is based on the observation of the estimator on size n samples drawn from the original sample. The two methods are presented, their principle is illustrated through their application to simple examples and to more complex epidemiological problems.
715 citations
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TL;DR: It is suggested that irrespective of the causes of their emergence, stress-induced mutations participate in adaptive evolution and could be a by-product of genetic strategies for improving survival under stress.
Abstract: The evolutionary significance of stress-induced mutagenesis was evaluated by studying mutagenesis in aging colonies (MAC) of Escherichia coli natural isolates. A large fraction of isolates exhibited a strong MAC, and the high MAC variability reflected the diversity of selective pressures in ecological niches. MAC depends on starvation, oxygen, and RpoS and adenosine 3,5-monophosphate regulons; thus it may be a by-product of genetic strategies for improving survival under stress. MAC could also be selected through beneficial mutations that it generates, as shown by computer modeling and the patterns of stressinducible and constitutive mutagenesis. We suggest that irrespective of the causes of their emergence, stress-induced mutations participate in adaptive
715 citations
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University of Helsinki1, University of Oulu2, University of Tampere3, Turku University Hospital4, University of Turku5, Hannover Medical School6, University of Cambridge7, Netherlands Cancer Institute8, Institute of Cancer Research9, University of Melbourne10, University of Erlangen-Nuremberg11, University of California, Los Angeles12, University of London13, King's College London14, Wellcome Trust Centre for Human Genetics15, Heidelberg University16, German Cancer Research Center17, French Institute of Health and Medical Research18, Copenhagen University Hospital19, University of Copenhagen20, Beckman Research Institute21, University of California, Irvine22, Technische Universität München23, University of Cologne24, Bosch25, University of Tübingen26, Ruhr University Bochum27, Karolinska Institutet28, University of Eastern Finland29, QIMR Berghofer Medical Research Institute30, Katholieke Universiteit Leuven31, University of Hamburg32, Mayo Clinic33, Cancer Council Victoria34, University of Southern California35, Laval University36, Oslo University Hospital37, The Breast Cancer Research Foundation38, Vanderbilt University39, Oulu University Hospital40, Lunenfeld-Tanenbaum Research Institute41, University of Toronto42, Leiden University Medical Center43, Erasmus University Rotterdam44, Erasmus University Medical Center45, University of Sheffield46, Pontifical Xavierian University47, Pomeranian Medical University48
TL;DR: It is suggested that loss-of-function mutations in RAD 51B are rare, but common variation at the RAD51B region is significantly associated with familial breast cancer risk.
Abstract: Common variation on 14q24.1, close to RAD51B, has been associated with breast cancer: rs999737 and rs2588809 with the risk of female breast cancer and rs1314913 with the risk of male breast cancer. The aim of this study was to investigate the role of RAD51B variants in breast cancer predisposition, particularly in the context of familial breast cancer in Finland. We sequenced the coding region of RAD51B in 168 Finnish breast cancer patients from the Helsinki region for identification of possible recurrent founder mutations. In addition, we studied the known rs999737, rs2588809, and rs1314913 SNPs and RAD51B haplotypes in 44,791 breast cancer cases and 43,583 controls from 40 studies participating in the Breast Cancer Association Consortium (BCAC) that were genotyped on a custom chip (iCOGS). We identified one putatively pathogenic missense mutation c.541C>T among the Finnish cancer patients and subsequently genotyped the mutation in additional breast cancer cases (n = 5259) and population controls (n = 3586) from Finland and Belarus. No significant association with breast cancer risk was seen in the meta-analysis of the Finnish datasets or in the large BCAC dataset. The association with previously identified risk variants rs999737, rs2588809, and rs1314913 was replicated among all breast cancer cases and also among familial cases in the BCAC dataset. The most significant association was observed for the haplotype carrying the risk-alleles of all the three SNPs both among all cases (odds ratio (OR): 1.15, 95% confidence interval (CI): 1.11-1.19, P = 8.88 x 10-16) and among familial cases (OR: 1.24, 95% CI: 1.16-1.32, P = 6.19 x 10-11), compared to the haplotype with the respective protective alleles. Our results suggest that loss-of-function mutations in RAD51B are rare, but common variation at the RAD51B region is significantly associated with familial breast cancer risk.
715 citations
Authors
Showing all 109539 results
Name | H-index | Papers | Citations |
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Guido Kroemer | 236 | 1404 | 246571 |
Pierre Chambon | 211 | 884 | 161565 |
Peer Bork | 206 | 697 | 245427 |
Ronald M. Evans | 199 | 708 | 166722 |
Raymond J. Dolan | 196 | 919 | 138540 |
Matthew Meyerson | 194 | 553 | 243726 |
Charles A. Dinarello | 190 | 1058 | 139668 |
Julie E. Buring | 186 | 950 | 132967 |
Tadamitsu Kishimoto | 181 | 1067 | 130860 |
Didier Raoult | 173 | 3267 | 153016 |
Giuseppe Remuzzi | 172 | 1226 | 160440 |
Zena Werb | 168 | 473 | 122629 |
Nahum Sonenberg | 167 | 647 | 104053 |
Philippe Froguel | 166 | 820 | 118816 |
Gordon J. Freeman | 164 | 579 | 105193 |