Institution
Brown University
Education•Providence, Rhode Island, United States•
About: Brown University is a education organization based out in Providence, Rhode Island, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 35778 authors who have published 90896 publications receiving 4471489 citations. The organization is also known as: brown.edu & Brown.
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TL;DR: The authors' analyses identified three molecular subclasses of oesophageal squamous cell carcinomas, but none showed evidence for an aetiological role of human papillomavirus and these data provide a framework to facilitate more rational categorization of these tumours and a foundation for new therapies.
Abstract: Oesophageal cancers are prominent worldwide; however, there are few targeted therapies and survival rates for these cancers remain dismal. Here we performed a comprehensive molecular analysis of 164 carcinomas of the oesophagus derived from Western and Eastern populations. Beyond known histopathological and epidemiologic distinctions, molecular features differentiated oesophageal squamous cell carcinomas from oesophageal adenocarcinomas. Oesophageal squamous cell carcinomas resembled squamous carcinomas of other organs more than they did oesophageal adenocarcinomas. Our analyses identified three molecular subclasses of oesophageal squamous cell carcinomas, but none showed evidence for an aetiological role of human papillomavirus. Squamous cell carcinomas showed frequent genomic amplifications of CCND1 and SOX2 and/or TP63, whereas ERBB2, VEGFA and GATA4 and GATA6 were more commonly amplified in adenocarcinomas. Oesophageal adenocarcinomas strongly resembled the chromosomally unstable variant of gastric adenocarcinoma, suggesting that these cancers could be considered a single disease entity. However, some molecular features, including DNA hypermethylation, occurred disproportionally in oesophageal adenocarcinomas. These data provide a framework to facilitate more rational categorization of these tumours and a foundation for new therapies.
1,289 citations
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TL;DR: On etudie les solutions regulieres non negatives de l'equation conformement invariante −Δu=u (n+2)/(n−2), u>0 dans une boule perforee, B 1 (0)\{0}⊂R n, n≥3, avec une singularite isolee a l'origine.
Abstract: On etudie les solutions regulieres non negatives de l'equation conformement invariante −Δu=u (n+2)/(n−2) , u>0 dans une boule perforee, B 1 (0)\{0}⊂R n , n≥3, avec une singularite isolee a l'origine
1,288 citations
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TL;DR: Computer modelling and histological findings showed that site of tearing was influenced by variation in the mechanical strength of cap tissue due to focal accumulation of foam cells, and the distribution of circumferential tensile stress across the intima was radically altered by atherosclerotic plaques.
1,281 citations
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01 Jan 19601,278 citations
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TL;DR: Evidence is provided that estrogen-induced Erk-1/-2 activation occurs independently of known estrogen receptors, but requires the expression of the G protein-coupled receptor homolog, GPR30.
Abstract: Estrogen rapidly activates the mitogen-activated protein kinases, Erk-1 and Erk-2, via an as yet unknown mechanism. Here, evidence is provided that estrogen-induced Erk-1/-2 activation occurs independently of known estrogen receptors, but requires the expression of the G protein-coupled receptor homolog, GPR30. We show that 17beta-estradiol activates Erk-1/-2 not only in MCF-7 cells, which express both estrogen receptor alpha (ER alpha) and ER beta, but also in SKBR3 breast cancer cells, which fail to express either receptor. Immunoblot analysis using GPR30 peptide antibodies showed that this estrogen response was associated with the presence of GPR30 protein in these cells. MDA-MB-231 breast cancer cells (ER alpha-, ER beta+) are GPR30 deficient and insensitive to Erk-1/-2 activation by 17beta-estradiol. Transfection of MDA-MB-231 cells with a GPR30 complementary DNA resulted in overexpression of GPR30 protein and conversion to an estrogen-responsive phenotype. In addition, GPR30-dependent Erk-1/-2 activation was triggered by ER antagonists, including ICI 182,780, yet not by 17alpha-estradiol or progesterone. Consistent with acting through a G protein-coupled receptor, estradiol signaling to Erk-1/-2 occurred via a Gbetagamma-dependent, pertussis toxin-sensitive pathway that required Src-related tyrosine kinase activity and tyrosine phosphorylation of tyrosine 317 of the Shc adapter protein. Reinforcing this idea, estradiol signaling to Erk-1/-2 was dependent upon trans-activation of the epidermal growth factor (EGF) receptor via release of heparan-bound EGF (HB-EGF). Estradiol signaling to Erk-1/-2 could be blocked by: 1) inhibiting EGF-receptor tyrosine kinase activity, 2) neutralizing HB-EGF with antibodies, or 3) down-modulating HB-EGF from the cell surface with the diphtheria toxin mutant, CRM-197. Our data imply that ER-negative breast tumors that continue to express GPR30 may use estrogen to drive growth factor-dependent cellular responses.
1,274 citations
Authors
Showing all 36143 results
Name | H-index | Papers | Citations |
---|---|---|---|
Walter C. Willett | 334 | 2399 | 413322 |
Robert Langer | 281 | 2324 | 326306 |
Robert M. Califf | 196 | 1561 | 167961 |
Eric J. Topol | 193 | 1373 | 151025 |
Joan Massagué | 189 | 408 | 149951 |
Joseph Biederman | 179 | 1012 | 117440 |
Gonçalo R. Abecasis | 179 | 595 | 230323 |
James F. Sallis | 169 | 825 | 144836 |
Steven N. Blair | 165 | 879 | 132929 |
Charles M. Lieber | 165 | 521 | 132811 |
J. S. Lange | 160 | 2083 | 145919 |
Christopher J. O'Donnell | 159 | 869 | 126278 |
Charles M. Perou | 156 | 573 | 202951 |
David J. Mooney | 156 | 695 | 94172 |
Richard J. Davidson | 156 | 602 | 91414 |