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
Papers
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TL;DR: By recapitulating local architectures that cells encounter in vivo, this work can elucidate and dissect the fundamental signal transduction pathways that control cell behavior in critical developmental, physiological, and pathological processes.
Abstract: The architecture of the extracellular matrix (ECM) directs cell behavior by providing spatial and mechanical cues to which cells respond. In addition to soluble chemical factors, physical interactions between the cell and ECM regulate primary cell processes, including differentiation, migration, and proliferation. Advances in microtechnology and, more recently, nanotechnology provide a powerful means to study the influence of the ECM on cell behavior. By recapitulating local architectures that cells encounter in vivo, we can elucidate and dissect the fundamental signal transduction pathways that control cell behavior in critical developmental, physiological, and pathological processes.
517 citations
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TL;DR: Optimal clinical efficacy will require testing of novel approaches targeting complete suppression of systemic and intracrine contributions to the prostatic androgen microenvironment.
Abstract: Androgen deprivation therapy (ADT) remains the primary treatment for advanced prostate cancer. The efficacy of ADT has not been rigorously evaluated by demonstrating suppression of prostatic androgen activity at the target tissue and molecular level. We determined the efficacy and consistency of medical castration in suppressing prostatic androgen levels and androgen-regulated gene expression. Androgen levels and androgen-regulated gene expression (by microarray profiling, quantitative reverse transcription-PCR, and immunohistochemistry) were measured in prostate samples from a clinical trial of short-term castration (1 month) using the gonadotropin-releasing hormone antagonist, Acyline, versus placebo in healthy men. To assess the effects of long-term ADT, gene expression measurements were evaluated at baseline and after 3, 6, and 9 months of neoadjuvant ADT in prostatectomy samples from men with localized prostate cancer. Medical castration reduced tissue androgens by 75% and reduced the expression of several androgen-regulated genes (NDRG1, FKBP5, and TMPRSS2). However, many androgen-responsive genes, including the androgen receptor (AR) and prostate-specific antigen (PSA), were not suppressed after short-term castration or after 9 months of neoadjuvant ADT. Significant heterogeneity in PSA and AR protein expression was observed in prostate cancer samples at each time point of ADT. Medical castration based on serum testosterone levels cannot be equated with androgen ablation in the prostate microenvironment. Standard androgen deprivation does not consistently suppress androgen-dependent gene expression. Suboptimal suppression of tumoral androgen activity may lead to adaptive cellular changes allowing prostate cancer cell survival in a low androgen environment. Optimal clinical efficacy will require testing of novel approaches targeting complete suppression of systemic and intracrine contributions to the prostatic androgen microenvironment.
516 citations
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TL;DR: Evaluated reconstitution of CMV-specific T-cell responses in 47 bone marrow transplant (BMT) recipients and suggest that a delay in recovery of these responses as a result of ganciclovir prophylaxis may contribute to the occurrence of late CMV disease.
515 citations
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TL;DR: This randomized trial suggests that continuous combined estrogen plus progestin therapy may increase the risk of ovarian cancer while producing endometrial cancer rates similar to placebo, and provides additional support for caution in the use of continuous combined hormones.
Abstract: ContextThe effects of continuous combined hormone therapy on gynecologic cancers
have not been investigated previously in a randomized trial setting.ObjectiveTo determine the possible associations of estrogen plus progestin on
gynecologic cancers and related diagnostic procedures.Design, Setting, and ParticipantsRandomized, double-blind, placebo-controlled trial of 16 608 postmenopausal
women, who had not had a hysterectomy at baseline and who had been recruited
from 40 US clinical centers between September 1993 and October 1998 (average
follow-up, 5.6 years).InterventionOne tablet per day containing 0.625 mg of conjugated equine estrogens
plus 2.5 mg of medroxyprogesterone acetate (n = 8506) or placebo (n = 8102).Main Outcome MeasureIncident invasive cancer of the ovary and endometrium.ResultsIn 5.6 years of follow-up, there were 32 cases of invasive ovarian cancer,
58 cases of endometrial cancer, 1 case of nonendometrial uterine cancer, 13
cases of cervical cancer, and 7 cases of other gynecologic cancers. The hazard
ratio (HR) for invasive ovarian cancer in women assigned to estrogen plus
progestin compared with placebo was 1.58 (95% confidence interval [CI], 0.77-3.24).
The HR for endometrial cancer was 0.81 (95% CI, 0.48-1.36). No appreciable
differences were found in the distributions of tumor histology, stage, or
grade for either cancer site. The incidence of other gynecologic cancers was
low and did not differ by randomization assignment. More women taking estrogen
plus progestin required endometrial biopsies (33% vs 6%; P<.001).ConclusionsThis randomized trial suggests that continuous combined estrogen plus
progestin therapy may increase the risk of ovarian cancer while producing
endometrial cancer rates similar to placebo. The increased burden of endometrial
biopsies required to assess vaginal bleeding further limits the acceptability
of this regimen. These data provide additional support for caution in the
use of continuous combined hormones.
515 citations
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TL;DR: Results suggest that the increase in transforming ability and kinase activity that occurred in the genesis of pp60v-src may have resulted from the loss of a tyrosine involved in negative regulation.
Abstract: The Rous sarcoma virus oncogene product, pp60v-src, transforms cultured fibroblasts but its corresponding proto-oncogene product, pp60c-src, does not. Both proteins are known to be protein-tyrosine kinases. Published results suggest that the kinase activity of pp60c-src is inhibited relative to that of pp60v-src, due perhaps to phosphorylation of a tyrosine in pp60c-src that is not phosphorylated in pp60v-src. In this study, it was observed that the tyrosine phosphorylated in pp60c-src is Tyr527, six residues from the COOH-terminus of the protein. The region of pp60c-src from residue 515 to the COOH-terminus, including Tyr527, has been replaced with a different sequence in pp60v-src. Thus, the increase in transforming ability and kinase activity that occurred in the genesis of pp60v-src may have resulted from the loss of a tyrosine involved in negative regulation.
515 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 |