Dean Billheimer

PMID: 15781645;Abstract:

ΔNp63α is a nuclear transcription factor that maintains epithelial progenitor cell populations, is overexpressed in several epithelial cancers, and can negatively regulate apoptosis. However, the mechanisms by which ΔNp63α promotes cell survival are unclear. ΔNp63α has been reported to act as a transcriptional repressor, but specific target genes directly repressed by ΔNp63α remain unidentified. Here, we present evidence that ΔNp63α functions to negatively regulate the proapoptotic protein IGFBP-3. Disruption of p63 expression in squamous epithelial cells increases IGFBP-3 expression, whereas ectopic expression of ΔNp63α down-regulates IGFBP-3. ΔNp63α binds to sites in the IGFBP-3 gene in vivo and can modulate transcription through these sites. Furthermore, ΔNp63α and IGFBP-3 expression patterns are inversely correlated in normal squamous epithelium and squamous cell carcinomas. These data suggest that IGFBP-3 is a target of transcriptional repression by ΔNp63α and that this repression represents a mechanism by which tumors that overexpress p63 may be protected from apoptosis. ©2005 American Association for Cancer Research.

PMID: 17827386;Abstract:

A prospective multicenter trial was conducted to evaluate the safety and feasibility of granulocyte colony-stimulating factor (G-CSF)-primed bone marrow (G-BM) in children receiving allogeneic bone marrow transplantation (BMT). A total of 42 children with a median age of 9.8 years (range, 0.8-17 years) were enrolled. Donors with median age of 9.2 years (range, 1.1-22 years) received 5 μg/kg per day of subcutaneous G-CSF for 5 consecutive days. BM was harvested on the fifth day. No donor experienced complications related to G-CSF administration or marrow harvest. Median nucleated (NC) and CD34 cells infused was 6.7 × 10⁸/kg (range, 2.4-18.5 × 10⁸/kg) and 7.4 × 10⁶/kg (range, 2-27.6 × 10⁶/kg), respectively. Neutrophil and platelet engraftment was at a median of 19 days (range, 13-28 days) and 20 days (range, 9-44 days), respectively. A total of 13 (32%) patients developed grade 2 graft-versus-host disease (GVHD), and 5 (13%) of 40 evaluable patients developed chronic GVHD (3 limited and 2 extensive). Higher cell dose was not associated with increased risk of acute or chronic GVHD. Overall survival and event-free survival at 2 years were 81% and 69%, respectively. Collection of G-BM from pediatric donors is safe, and can result in high NC and CD34 cell doses that facilitate engraftment after myeloablative BMT without a discernable increase in the risk of GVHD. © 2007 by The American Society of Hematology.