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.

Factors that influence collection and engraftment of autologous peripheral-blood stem cells.

Abstract: PURPOSETo analyze factors that affect the collection of peripheral-blood stem cells (PBSC) before transplant and the tempo of engraftment after transplant.PATIENTS AND METHODSA consecutive series of 243 patients with breast cancer (n = 87), malignant lymphoma (n = 90), multiple myeloma (n = 32), or other malignancies (n = 34) had PBSC collected following stimulation with colony-stimulating factors (CSFs) or after chemotherapy followed by CSF. Infusion of PBSC was performed following myeloablative chemotherapy with chemotherapy with or without total-body irradiation (TBI). Postinfusion CSFs were administered to 72 patients. An analysis of factors that influence CD34+ cell yield was performed by linear regression. Cox regression analysis was used to determine factors that affect the kinetics of granulocyte and platelet recovery following infusion of PBSC.RESULTSMobilization with chemotherapy followed by CSF, a diagnosis of breast cancer, absence of marrow disease, no prior history of radiation therapy, and ...

Loss of normal p53 function confers sensitization to Taxol by increasing G2/M arrest and apoptosis

Abstract: The anticancer agent paclitaxel (Taxol) stabilizes tubulin polymerization resulting in arrest in mitosis and apoptotic cell death. Normal human fibroblasts depleted of functional p53 by SV40 T antigen or HPV-16 E6, and primary embryo fibroblasts from p53 null mice showed seven- to ninefold increased cytotoxicity by paclitaxel. Reduced levels of p53 correlated with increased G2/M phase arrest, micronucleation, and p53-independent paclitaxel-induced apoptosis. Surviving cells with intact p53 progressed through mitosis and transiently accumulated in the subsequent G1 phase, coincident with increased p53 and p21cip1,waf1 protein levels. These results are in contrast to studies linking p53 loss with resistance to DNA damaging anticancer agents.

Sequencing of 53,831 diverse genomes from the NHLBI TOPMed Program

Abstract: Summary paragraph The Trans-Omics for Precision Medicine (TOPMed) program seeks to elucidate the genetic architecture and disease biology of heart, lung, blood, and sleep disorders, with the ultimate goal of improving diagnosis, treatment, and prevention. The initial phases of the program focus on whole genome sequencing of individuals with rich phenotypic data and diverse backgrounds. Here, we describe TOPMed goals and design as well as resources and early insights from the sequence data. The resources include a variant browser, a genotype imputation panel, and sharing of genomic and phenotypic data via dbGaP. In 53,581 TOPMed samples, >400 million single-nucleotide and insertion/deletion variants were detected by alignment with the reference genome. Additional novel variants are detectable through assembly of unmapped reads and customized analysis in highly variable loci. Among the >400 million variants detected, 97% have frequency

Identification of a new family of tissue-specific basic helix-loop-helix proteins with a two-hybrid system.

Abstract: With modified two-hybrid technology, we have isolated a member of a new family of basic helix-loop-helix (bHLH) transcription factors. Thing1 (Th1) was identified in a screen of a mouse embryo cDNA library as a partner for theDrosophilaE protein daughterless. RNA in situ hybridization and reverse transcriptase-PCR demonstrate a stage- and tissue-specific distribution for the expression of Th1. Although tissue specific, the expression pattern ofTh1is fairly complex. During development,Th1mRNA is widely expressed in extraembryonictissues,portionsoftheheart,autonomicganglia,thegut,andpharyngealarches.Atembryonicday7.5 (E7.5), extraembryonic derivatives show robust Th1 expression. By E8.5, expression in the embryonic heart becomesdetectable.Duringthenext2daysofdevelopment,thesignalalsoincludesgutandpharyngealarches. Predominant expression at E13.5 is in neural crest derivatives, especially the autonomic nervous system and adrenal medulla. Expression ofTh1persists in the adult, in which it is localized to the smooth muscle cells of the gut. In vitro, Th1 protein recognizes a set of DNA sites that are more degenerate than has been determined for other bHLH factors, indicating a reduced binding specificity. Transient transfection of NIH 3T3 cells with GAL4-Th1 fusions reveals a repression activity mediated by the Th1 bHLH domain. In combination, these properties define Th1 as a new bHLH protein with a unique set of properties. Duringdevelopment,specificgeneticprogramsareactivated by transcription factors which are often stage and tissue specific in their distribution. Understanding the combinatorial code of factors which defines each cell fate during the differentiation process requires identification of new factors with restricted spatial activity. One group of factors with pivotal roles during development are the basic helix-loop-helix (bHLH) proteins. These factors are important in differentiation processes as diverse as skeletal myogenesis, neurogenesis, andhematopoiesis(forreviews,seereferences2,12,13,43,59,

Trans -acting regulatory variation in Saccharomyces cerevisiae and the role of transcription factors

Abstract: Natural genetic variation can cause significant differences in gene expression, but little is known about the polymorphisms that affect gene regulation. We analyzed regulatory variation in a cross between laboratory and wild strains of Saccharomyces cerevisiae. Clustering and linkage analysis defined groups of coregulated genes and the loci involved in their regulation. Most expression differences mapped to trans-acting loci. Positional cloning and functional assays showed that polymorphisms in GPA1 and AMN1 affect expression of genes involved in pheromone response and daughter cell separation, respectively. We also asked whether particular classes of genes were more likely to contain trans-regulatory polymorphisms. Notably, transcription factors showed no enrichment, and trans-regulatory variation seems to be broadly dispersed across classes of genes with different molecular functions.