Institution
Indiana University
Education•Bloomington, Indiana, United States•
About: Indiana University is a education organization based out in Bloomington, Indiana, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 64480 authors who have published 150058 publications receiving 6392902 citations. The organization is also known as: Indiana University system & indiana.edu.
Topics: Population, Poison control, Context (language use), Health care, Cancer
Papers published on a yearly basis
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TL;DR: Since ER inhibits the constitutive as well as inducible activation function of NF-kappaB in a dose-dependent manner, it is proposed that breast cancers that lack functional ER overexpress NF- kappaB-regulated genes.
Abstract: Breast cancers often progress from a hormone-dependent, nonmetastatic, antiestrogen-sensitive phenotype to a hormone-independent, antiestrogen- and chemotherapy-resistant phenotype with highly invasive and metastatic growth properties. This progression is usually accompanied by altered function of the estrogen receptor (ER) or outgrowth of ER-negative cancer cells. To understand the molecular mechanisms responsible for metastatic growth of ER-negative breast cancers, the activities of the transcription factor NF-kappaB (which modulates the expression of genes involved in cell proliferation, differentiation, apoptosis, and metastasis) were compared in ER-positive (MCF-7 and T47-D) and ER-negative (MDA-MB-231 and MDA-MB-435) human breast cancer cell lines. NF-kappaB, which is usually maintained in an inactive state by protein-protein interaction with inhibitor IkappaBs, was found to be constitutively active in ER-negative breast cancer cell lines. Constitutive DNA binding of NF-kappaB was also observed with extracts from ER-negative, poorly differentiated primary breast tumors. Progression of the rat mammary carcinoma cell line RM22-F5 from an ER-positive, nonmalignant phenotype (E phenotype) to an ER-negative, malignant phenotype (F phenotype) was also accompanied by constitutive activation of NF-kappaB. Analysis of individual subunits of NF-kappaB revealed that all ER-negative cell lines, including RM22-F5 cells of F phenotype, contain a unique 37-kDa protein which is antigenically related to the RelA subunit. Cell-type-specific differences in IkappaB alpha, -beta, and -gamma were also observed. In transient-transfection experiments, constitutive activity of an NF-kappaB-dependent promoter was observed in MDA-MB-231 and RM22-F5 cells of F phenotype, and this activity was efficiently repressed by cotransfected ER. Since ER inhibits the constitutive as well as inducible activation function of NF-kappaB in a dose-dependent manner, we propose that breast cancers that lack functional ER overexpress NF-kappaB-regulated genes. Furthermore, since recent data indicate that NF-kappaB protects cells from tumor necrosis factor alpha-, ionizing radiation-, and chemotherapeutic agent daunorubicin-mediated apoptosis, our results provide an explanation for chemotherapeutic resistance in ER-negative breast cancers.
859 citations
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Indiana University1, Buck Institute for Research on Aging2, University of California, San Francisco3, University of California, Santa Cruz4, Colorado State University5, University of Colorado Denver6, Icahn School of Medicine at Mount Sinai7, University of California, Berkeley8, European Bioinformatics Institute9, University of Bologna10, University of Missouri11, University of Bristol12, University of Helsinki13, University College London14, Centre for Development of Advanced Computing15, Purdue University16, Baylor College of Medicine17, Royal Holloway, University of London18, Technische Universität München19, University of Turku20, Queen's University21, University UCINF22, Max Planck Society23, Imperial College London24, Wageningen University and Research Centre25, Nestlé26, Fudan University27, University of Padua28, Temple University29, University of Geneva30, Swiss Institute of Bioinformatics31, Hebrew University of Jerusalem32, Miami University33
TL;DR: Today's best protein function prediction algorithms substantially outperform widely used first-generation methods, with large gains on all types of targets, and there is considerable need for improvement of currently available tools.
Abstract: Automated annotation of protein function is challenging. As the number of sequenced genomes rapidly grows, the overwhelming majority of protein products can only be annotated computationally. If computational predictions are to be relied upon, it is crucial that the accuracy of these methods be high. Here we report the results from the first large-scale community-based critical assessment of protein function annotation (CAFA) experiment. Fifty-four methods representing the state of the art for protein function prediction were evaluated on a target set of 866 proteins from 11 organisms. Two findings stand out: (i) today's best protein function prediction algorithms substantially outperform widely used first-generation methods, with large gains on all types of targets; and (ii) although the top methods perform well enough to guide experiments, there is considerable need for improvement of currently available tools.
859 citations
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TL;DR: Evidence demonstrates an association between a number of single nucleotide polymorphisms in oxidative DNA repair genes and antioxidant genes with human cancer susceptibility and the resultant altered gene expression patterns evoked by ROS contribute to the carcinogenesis process.
Abstract: Carcinogenesis is a multistep process involving mutation and the subsequent selective clonal expansion of the mutated cell. Chemical and physical agents including those that induce reative oxygen species can induce and/or modulate this multistep process. Several modes of action by which carcinogens induce cancer have been identified, including through production of reactive oxygen species (ROS). Oxidative damage to cellular macromolecules can arise through overproduction of ROS and faulty antioxidant and/or DNA repair mechanisms. In addition, ROS can stimulate signal transduction pathways and lead to activation of key transcription factors such as Nrf2 and NF-kappaB. The resultant altered gene expression patterns evoked by ROS contribute to the carcinogenesis process. Recent evidence demonstrates an association between a number of single nucleotide polymorphisms (SNPs) in oxidative DNA repair genes and antioxidant genes with human cancer susceptibility. These aspects of ROS biology will be discussed in the context of their relationship to carcinogenesis.
859 citations
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TL;DR: The guideline includes data on the epidemiology, clinical features, diagnosis, and treatment of many viral, bacterial, fungal, protozoal, and helminthic etiologies of encephalitis and provides information on when specific etiologic agents should be considered in individual patients with encephalopathy.
Abstract: Guidelines for the diagnosis and treatment of patients with encephalitis were prepared by an Expert Panel of the Infectious Diseases Society of America. The guidelines are intended for use by health care providers who care for patients with encephalitis. The guideline includes data on the epidemiology, clinical features, diagnosis, and treatment of many viral, bacterial, fungal, protozoal, and helminthic etiologies of encephalitis and provides information on when specific etiologic agents should be considered in individual patients with encephalitis.
858 citations
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TL;DR: The differential environmental fates and toxicities of various hexachlorocyclohexane (HCH) isomers including lindane and isomers in the technical mixture will be the focus of this review.
Abstract: The differential environmental fates and toxicities of the various hexachlorocyclohexane (HCH) isomers including lindane and isomers in the technical mixture will be the focus of this review. HCHs are one of the most widely used and most readily detected organochlorine pesticides in environmental samples. The relatively high volatility of HCH has led to global transport, even into formerly pristine locations such as the Arctic. Certain HCHs cause central nervous system, reproductive, and endocrine damage. Because γ-HCH is rapidly metabolized, the β-HCH isomer is consistently found in higher concentrations in human fat, blood, and breast milk. In contrast, α- and γ-HCH are the most prevalent isomers in soil, water, and air samples. The ratio of the α- to γ-isomers can be used to track global transport of HCHs. A new area of HCH research focuses on the selective degradation of the two α-HCH enantiomers in various environmental matrices. These HCH issues and recommendations for future HCH research are presen...
858 citations
Authors
Showing all 64884 results
Name | H-index | Papers | Citations |
---|---|---|---|
Frank B. Hu | 250 | 1675 | 253464 |
Stuart H. Orkin | 186 | 715 | 112182 |
Bruce M. Spiegelman | 179 | 434 | 158009 |
David R. Williams | 178 | 2034 | 138789 |
D. M. Strom | 176 | 3167 | 194314 |
Markus Antonietti | 176 | 1068 | 127235 |
Lei Jiang | 170 | 2244 | 135205 |
Brenda W.J.H. Penninx | 170 | 1139 | 119082 |
Nahum Sonenberg | 167 | 647 | 104053 |
Carl W. Cotman | 165 | 809 | 105323 |
Yang Yang | 164 | 2704 | 144071 |
Jaakko Kaprio | 163 | 1532 | 126320 |
Ralph A. DeFronzo | 160 | 759 | 132993 |
Gavin Davies | 159 | 2036 | 149835 |
Tyler Jacks | 158 | 463 | 115172 |