Showing papers by "Edward F. Srour published in 2006"
TL;DR: Ritonavir inhibits breast cancer growth in part by inhibiting Hsp90 substrates, including Akt, and its efficacy may be increased by sustained exposure or HSp90 RNA interference.
Abstract: Purpose: These studies were designed to determine whether ritonavir inhibits breast cancer in vitro and in vivo and, if so, how. Experimental Design: Ritonavir effects on breast cancer cell growth were studied in the estrogen receptor (ER)–positive lines MCF7 and T47D and in the ER-negative lines MDA-MB-436 and MDA-MB-231. Effects of ritonavir on Rb-regulated and Akt-mediated cell proliferation were studied. Ritonavir was tested for inhibition of a mammary carcinoma xenograft. Results: ER-positive estradiol-dependent lines (IC 50 , 12-24 μmol/L) and ER-negative (IC 50 , 45 μmol/L) lines exhibit ritonavir sensitivity. Ritonavir depletes ER-α levels notably in ER-positive lines. Ritonavir causes G 1 arrest, depletes cyclin-dependent kinases 2, 4, and 6 and cyclin D 1 but not cyclin E, and depletes phosphorylated Rb and Ser 473 Akt. Ritonavir induces apoptosis independent of G 1 arrest, inhibiting growth of cells that have passed the G 1 checkpoint. Myristoyl-Akt, but not activated K-Ras, rescues ritonavir inhibition. Ritonavir inhibited a MDA-MB-231 xenograft and intratumoral Akt activity at a clinically attainable serum C max of 22 ± 8 μmol/L. Because heat shock protein 90 (Hsp90) substrates are depleted by ritonavir, ritonavir effects on Hsp90 were tested. Ritonavir binds Hsp90 ( K D , 7.8 μmol/L) and partially inhibits its chaperone function. Ritonavir blocks association of Hsp90 with Akt and, with sustained exposure, notably depletes Hsp90. Stably expressed Hsp90α short hairpin RNA also depletes Hsp90, inhibiting proliferation and sensitizing breast cancer cells to low ritonavir concentrations. Conclusions: Ritonavir inhibits breast cancer growth in part by inhibiting Hsp90 substrates, including Akt. Ritonavir may be of interest for breast cancer therapeutics and its efficacy may be increased by sustained exposure or Hsp90 RNA interference.
103 citations
TL;DR: This chapter reviews information on the clinical and biological properties of hematopoietic stem and progenitor cells, as well as the biology of endothelial progenitors, and serves as a source for the methods used to detect and quantitate these important functional cells.
Abstract: Cord blood has served as a source of hematopoietic stem and progenitor cells for successful repopulation of the blood cell system in patients with malignant and nonmalignant disorders. It was information on these rare immature cells in cord blood that led to the first use of cord blood for transplantation. Further information on these cells and how they can be manipulated both in vitro and in vivo will likely enhance the utility and broadness of applicability of cord blood for treatment of human disease. This chapter reviews information on the clinical and biological properties of hematopoietic stem and progenitor cells, as well as the biology of endothelial progenitor cells, and serves as a source for the methods used to detect and quantitate these important functional cells. Specifically, methods are presented for enumerating human cord blood myeloid progenitor cells, including granulocyte-macrophage (CFU-GM), erythroid (BFU-E), and multipotential (CFU-GEMM or CFU-Mix) progenitors, and their replating potential; hematopoietic stem cells, as assessed in vitro for long-term culture-initiating cells (LTC-ICs), cobblestone area-forming cells (CAFCs), and myeloid-lymphoid-initiating cells (ML-ICs), and as assessed in vivo for nonobese diabetic (NOD)/severe combined immunodeficient (SCID) mouse repopulating cells (SRCs); and high and low proliferative potential endothelial progenitor cells (EPCs).
81 citations
TL;DR: The data suggest that RMGT of hematopoietic cells may compromise their homing potential and implicate transduction-induced reduced homing in the observed low engraftment of retrovirally transduced CD34(+) cells.
28 citations
TL;DR: It is concluded that SM- cells are inherently predisposed to undergo cardiac differentiation and are enriched in markers of pluripotency.
22 citations
TL;DR: CXCR4 may influence the immune system under physiologic and pathologic conditions through negative regulation of MHC class II expression, possibly through PKA and SRC kinase.
20 citations
TL;DR: It is demonstrated that phenotypically homogenous skeletal muscle progenitor cells defined as Lin−CD45−CD117−CD90+ cells express neural stem cell markers and are responsive to neural induction signals.
Abstract: Skeletal muscle contains heterogenous progenitor cells that give rise to muscle, hematopoietic cells and bone. The exact phenotypic definition of skeletal muscle progenitor cells has not been fully elucidated nor the potential of these cells to differentiate into neurons. Here, we demonstrate that phenotypically homogenous skeletal muscle progenitor cells defined as Lin - CD45 - CDI17 - CD90 + cells express neural stem cell markers and are responsive to neural induction signals. When exposed to neural induction medium containing basic fibroblast growth factor and brain-derived neurotrophic factor, skeletal muscle progenitor cells dramatically changed their cell morphology, became postmitotic and began expressing neuronal markers. These results reveal unexpected potentials of muscle progenitor cells and suggest that these cells may potentially be used in cell-based therapies to replace damaged neurons.
18 citations