Fred Hutchinson Cancer Research Center

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.

Editing T cell specificity towards leukemia by zinc finger nucleases and lentiviral gene transfer

Abstract: Engineered T cells expressing a tumor antigen specific T cell receptor (TCR) have shown promise for cancer immunotherapy. However, the introduced TCR chains can pair with the endogenous TCR chains in T cells, and in mice, these mismatched TCRs can cause a lethal autoimmune reaction. Provasi et al. now show that they can eliminate expression of the endogenous TCR chains using zinc finger nucleases and express only the desired exogenous TCR by lentiviral transduction. The resultant TCR-edited lymphocytes showed tumor specificity without the risk of off-target toxicity.

Low-fat dietary pattern and weight change over 7 years: the Women's Health Initiative Dietary Modification Trial.

Abstract: ContextObesity in the United States has increased dramatically during the past several decades. There is debate about optimum calorie balance for prevention of weight gain, and proponents of some low-carbohydrate diet regimens have suggested that the increasing obesity may be attributed, in part, to low-fat, high-carbohydrate diets.ObjectivesTo report data on body weight in a long-term, low-fat diet trial for which the primary end points were breast and colorectal cancer and to examine the relationships between weight changes and changes in dietary components.Design, Setting, and ParticipantsRandomized intervention trial of 48 835 postmenopausal women in the United States who were of diverse backgrounds and ethnicities and participated in the Women's Health Initiative Dietary Modification Trial; 40% (19 541) were randomized to the intervention and 60% (29 294) to a control group. Study enrollment was between 1993 and 1998, and this analysis includes a mean follow-up of 7.5 years (through August 31, 2004).InterventionsThe intervention included group and individual sessions to promote a decrease in fat intake and increases in vegetable, fruit, and grain consumption and did not include weight loss or caloric restriction goals. The control group received diet-related education materials.Main Outcome MeasureChange in body weight from baseline to follow-up.ResultsWomen in the intervention group lost weight in the first year (mean of 2.2 kg, P<.001) and maintained lower weight than control women during an average 7.5 years of follow-up (difference, 1.9 kg, P<.001 at 1 year and 0.4 kg, P = .01 at 7.5 years). No tendency toward weight gain was observed in intervention group women overall or when stratified by age, ethnicity, or body mass index. Weight loss was greatest among women in either group who decreased their percentage of energy from fat. A similar but lesser trend was observed with increases in vegetable and fruit servings, and a nonsignificant trend toward weight loss occurred with increasing intake of fiber.ConclusionA low-fat eating pattern does not result in weight gain in postmenopausal women.Clinical Trial RegistrationClinicalTrials.gov Identifier: NCT00000611

Transcriptional outputs of the Caenorhabditis elegans forkhead protein DAF-16.

Abstract: In Caenorhabditis elegans, the forkhead protein DAF-16 transduces insulin-like signals that regulate larval development and adult lifespan. To identify DAF-16-dependent transcriptional alterations that occur in a long-lived C. elegans strain, we used cDNA microarrays and genomic analysis to identify putative direct and indirect DAF-16 transcriptional target genes. Our analysis suggests that DAF-16 action regulates a wide range of physiological responses by altering the expression of genes involved in metabolism, energy generation and cellular stress responses. Furthermore, we observed a large overlap between DAF-16-dependent transcription and genes normally expressed in the long-lived dauer larval stage. Finally, we examined the in vivo role of 35 of these target genes by RNA-mediated interference and identified one gene encoding a putative protease that is necessary for the daf-2 Age phenotype.

Reduction in Late Mortality among 5-Year Survivors of Childhood Cancer.

Abstract: BackgroundAmong patients in whom childhood cancer was diagnosed in the 1970s and 1980s, 18% of those who survived for 5 years died within the subsequent 25 years. In recent decades, cancer treatments have been modified with the goal of reducing life-threatening late effects. MethodsWe evaluated late mortality among 34,033 patients in the Childhood Cancer Survivor Study cohort who survived at least 5 years after childhood cancer (i.e., cancer diagnosed before the age of 21 years) for which treatment was initiated during the period from 1970 through 1999. The median follow-up was 21 years (range, 5 to 38). We evaluated demographic and disease factors that were associated with death from health-related causes (i.e., conditions that exclude recurrence or progression of the original cancer and external causes but include the late effects of cancer therapy) using cumulative incidence and piecewise exponential models to estimate relative rates and 95% confidence intervals. ResultsOf the 3958 deaths that occurred...