Institution
Fred Hutchinson Cancer Research Center
Nonprofit•Cape Town, South Africa•
About: Fred Hutchinson Cancer Research Center is a nonprofit organization based out in Cape Town, South Africa. It is known for research contribution in the topics: Population & Transplantation. The organization has 12322 authors who have published 30954 publications receiving 2288772 citations. The organization is also known as: Fred Hutch & The Hutch.
Topics: Population, Transplantation, Cancer, Breast cancer, Prostate cancer
Papers published on a yearly basis
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TL;DR: Results provide further evidence that in all eukaryotes assembly of a cyclin-Cdk complex is an important step in the biochemical pathway that controls cell proliferation during G1.
Abstract: Human cyclin E, originally identified on the basis of its ability to function as a G1 cyclin in budding yeast, associated with a cell cycle-regulated protein kinase in human cells. The cyclin E-associated kinase activity peaked during G1, before the appearance of cyclin A, and was diminished during exit from the cell cycle after differentiation or serum withdrawal. The major cyclin E-associated kinase in human cells was Cdk2 (cyclin-dependent kinase 2). The abundance of the cyclin E protein and the cyclin E-Cdk2 complex was maximal in G1 cells. These results provide further evidence that in all eukaryotes assembly of a cyclin-Cdk complex is an important step in the biochemical pathway that controls cell proliferation during G1.
1,058 citations
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TL;DR: This review draws on empirical studies in humans and Drosophila, as well as simulation studies, to assess the current state of knowledge about patterns of LD, and consider the implications for the use of LD as a mapping tool.
Abstract: Particular alleles at neighbouring loci tend to be co-inherited. For tightly linked loci, this might lead to associations between alleles in the population — a property known as linkage disequilibrium (LD). LD has recently become the focus of intense study in the hope that it might facilitate the mapping of complex disease loci through whole-genome association studies. This approach depends crucially on the patterns of LD in the human genome. In this review, we draw on empirical studies in humans and Drosophila, as well as simulation studies, to assess the current state of knowledge about patterns of LD, and consider the implications for the use of LD as a mapping tool.
1,053 citations
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Yeshiva University1, Wayne State University2, University of Florida3, University of North Carolina at Chapel Hill4, Fred Hutchinson Cancer Research Center5, National Institutes of Health6, Medical College of Wisconsin7, Rush University Medical Center8, Rutgers University9, George Washington University10, Ohio State University11
TL;DR: Excess risk for all strokes attributed to estrogen plus progestin appeared to be present in all subgroups of women examined, and excess risk of all stroke was apparent in all age groups, in all categories of baseline stroke risk, and in women with and without hypertension, prior history of cardiovascular disease, use of hormones, statins, or aspirin.
Abstract: ContextThe Women's Health Initiative (WHI) trial of estrogen plus progestin
was stopped early because of adverse effects, including an increased risk
of stroke in the estrogen plus progestin group.ObjectiveTo assess the effect of estrogen plus progestin on ischemic and hemorrhagic
stroke and in subgroups, and to determine whether the effect of estrogen plus
progestin was modified by baseline levels of blood biomarkers.DesignMulticenter double-blind, placebo-controlled, randomized clinical trial
involving 16 608 women aged 50 through 79 years with an average follow-up
of 5.6 years. Baseline levels of blood-based markers of inflammation, thrombosis,
and lipid levels were measured in the first 140 centrally confirmed stroke
cases and 513 controls.InterventionsParticipants received 0.625 mg/d of conjugated equine estrogen plus
2.5 mg/d of medroxyprogesterone acetate (n = 8506) or placebo (n = 8102).Main Outcome MeasuresOverall strokes and stroke subtype and severity were centrally adjudicated
by stroke neurologists.ResultsOne hundred fifty-one patients (1.8%) in the estrogen plus progestin
and 107 (1.3%) in the placebo groups had strokes. Overall 79.8% of strokes
were ischemic. For combined ischemic and hemorrhagic strokes, the intention-to-treat
hazard ratio (HR) for estrogen plus progestin vs placebo was 1.31 (95% confidence
interval [CI], 1.02-1.68); with adjustment for adherence, the HR was 1.50
(95% CI, 1.08-2.08). The HR for ischemic stroke was 1.44 (95% CI, 1.09-1.90)
and for hemorrhagic stroke, 0.82 (95% CI, 0.43-1.56). Point estimates of the
HRs indicate that excess risk of all stroke was apparent in all age groups,
in all categories of baseline stroke risk, and in women with and without hypertension,
prior history of cardiovascular disease, use of hormones, statins, or aspirin.
Other risk factors for stroke, including smoking, blood pressure, diabetes,
lower use of vitamin C supplements, blood-based biomarkers of inflammation,
higher white blood cell count, and higher hematocrit levels did not modify
the effect of estrogen plus progestin on stroke risk.ConclusionsEstrogen plus progestin increases the risk of ischemic stroke in generally
healthy postmenopausal women. Excess risk for all strokes attributed to estrogen
plus progestin appeared to be present in all subgroups of women examined.
1,052 citations
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University of California, San Francisco1, Harvard University2, University of Paris-Sud3, Université de Montréal4, Radboud University Nijmegen5, Charité6, University of Texas MD Anderson Cancer Center7, Hebron University8, University of Colorado Denver9, Fred Hutchinson Cancer Research Center10, University of Western Sydney11, Institute of Cancer Research12, Janssen Pharmaceutica13, Memorial Sloan Kettering Cancer Center14
TL;DR: Treatment with abiraterone acetate prolonged overall survival compared with prednisone alone by a margin that was both clinically and statistically significant, and further support the favourable safety profile of abiraton acetate in patients with chemotherapy-naive metastatic castration-resistant prostate cancer.
Abstract: Summary Background Abiraterone acetate plus prednisone significantly improved radiographic progression-free survival compared with placebo plus prednisone in men with chemotherapy-naive castration-resistant prostate cancer at the interim analyses of the COU-AA-302 trial. Here, we present the prespecified final analysis of the trial, assessing the effect of abiraterone acetate plus prednisone on overall survival, time to opiate use, and use of other subsequent therapies. Methods In this placebo-controlled, double-blind, randomised phase 3 study, 1088 asymptomatic or mildly symptomatic patients with chemotherapy-naive prostate cancer stratified by Eastern Cooperative Oncology performance status (0 vs 1) were randomly assigned with a permuted block allocation scheme via a web response system in a 1:1 ratio to receive either abiraterone acetate (1000 mg once daily) plus prednisone (5 mg twice daily; abiraterone acetate group) or placebo plus prednisone (placebo group). Coprimary endpoints were radiographic progression-free survival and overall survival analysed in the intention-to-treat population. The study is registered with ClinicalTrials.gov, number NCT00887198. Findings At a median follow-up of 49·2 months (IQR 47·0–51·8), 741 (96%) of the prespecified 773 death events for the final analysis had been observed: 354 (65%) of 546 patients in the abiraterone acetate group and 387 (71%) of 542 in the placebo group. 238 (44%) patients initially receiving prednisone alone subsequently received abiraterone acetate plus prednisone as crossover per protocol (93 patients) or as subsequent therapy (145 patients). Overall, 365 (67%) patients in the abiraterone acetate group and 435 (80%) in the placebo group received subsequent treatment with one or more approved agents. Median overall survival was significantly longer in the abiraterone acetate group than in the placebo group (34·7 months [95% CI 32·7–36·8] vs 30·3 months [28·7–33·3]; hazard ratio 0·81 [95% CI 0·70–0·93]; p=0·0033). The most common grade 3–4 adverse events of special interest were cardiac disorders (41 [8%] of 542 patients in the abiraterone acetate group vs 20 [4%] of 540 patients in the placebo group), increased alanine aminotransferase (32 [6%] vs four [ vs 17 [3%]). Interpretation In this randomised phase 3 trial with a median follow-up of more than 4 years, treatment with abiraterone acetate prolonged overall survival compared with prednisone alone by a margin that was both clinically and statistically significant. These results further support the favourable safety profile of abiraterone acetate in patients with chemotherapy-naive metastatic castration-resistant prostate cancer. Funding Janssen Research & Development.
1,041 citations
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National Institutes of Health1, University of British Columbia2, University of Nebraska Medical Center3, University of Oslo4, University of Barcelona5, University of Würzburg6, Oregon Health & Science University7, University of Arizona8, University of Rochester9, Fred Hutchinson Cancer Research Center10
TL;DR: Gene expression profiling strongly supported a relationship between PMBL and Hodgkin lymphoma: over one third of the genes that were more highly expressed in PMBL than in other DLBCLs were also characteristically expressed in Hodgkinymphoma cells.
Abstract: Using current diagnostic criteria, primary mediastinal B cell lymphoma (PMBL) cannot be distinguished from other types of diffuse large B cell lymphoma (DLBCL) reliably. We used gene expression profiling to develop a more precise molecular diagnosis of PMBL. PMBL patients were considerably younger than other DLBCL patients, and their lymphomas frequently involved other thoracic structures but not extrathoracic sites typical of other DLBCLs. PMBL patients had a relatively favorable clinical outcome, with a 5-yr survival rate of 64% compared with 46% for other DLBCL patients. Gene expression profiling strongly supported a relationship between PMBL and Hodgkin lymphoma: over one third of the genes that were more highly expressed in PMBL than in other DLBCLs were also characteristically expressed in Hodgkin lymphoma cells. PDL2, which encodes a regulator of T cell activation, was the gene that best discriminated PMBL from other DLBCLs and was also highly expressed in Hodgkin lymphoma cells. The genomic loci for PDL2 and several neighboring genes were amplified in over half of the PMBLs and in Hodgkin lymphoma cell lines. The molecular diagnosis of PMBL should significantly aid in the development of therapies tailored to this clinically and pathogenetically distinctive subgroup of DLBCL.
1,039 citations
Authors
Showing all 12368 results
Name | H-index | Papers | Citations |
---|---|---|---|
Walter C. Willett | 334 | 2399 | 413322 |
Robert Langer | 281 | 2324 | 326306 |
Meir J. Stampfer | 277 | 1414 | 283776 |
JoAnn E. Manson | 270 | 1819 | 258509 |
David J. Hunter | 213 | 1836 | 207050 |
Peer Bork | 206 | 697 | 245427 |
Eric Boerwinkle | 183 | 1321 | 170971 |
Ruedi Aebersold | 182 | 879 | 141881 |
Bruce M. Psaty | 181 | 1205 | 138244 |
Aaron R. Folsom | 181 | 1118 | 134044 |
David Baker | 173 | 1226 | 109377 |
Frederick W. Alt | 171 | 577 | 95573 |
Lily Yeh Jan | 162 | 467 | 73655 |
Yuh Nung Jan | 162 | 460 | 74818 |
Charles N. Serhan | 158 | 728 | 84810 |