Cyclophosphamide plus granulocyte-colony stimulating factor for hematopoietic stem cell mobilization in patients with multiple myeloma.

We retrospectively reviewed the results of cyclophosphamide (3 g/m(2) ), doxorubicin and dexamethasone plus granulocyte-colony stimulating factor (G-CSF) (ID-CY/DOX group), low-dose cyclophosphamide (2 g/m(2) ) plus G-CSF (LD-CY group) and G-CSF alone (G-CSF group) for stem cell mobilization in patients with multiple myeloma. A total of 89 patients with 93 mobilizations were included. Apheresis was started when total white blood cell (WBC) count >10 × 10(9) /L for ID-CY/DOX and LD-CY groups and after eight doses of G-CSF (5 µg/kg twice daily) for G-CSF group. For five mobilizations in ID-CY/DOX group, the rate of successful mobilization (≥4.0 × 10(6) /kg CD34+ cells) was 80%. For 78 mobilizations in LD-CY group, the successful rate was 80.8%. For 10 mobilizations in the G-CSF group, the successful rate was 50%. The mean yield of CD34+ cells was higher in ID-CY/DOX and LD-CY groups as compared with that in G-CSF group (P = 0.026 and 0.020, respectively). There was no difference in the yield of CD34+ cells between ID-CY/DOX and LD-CY groups (P = 0.831). After autologous stem cell transplantation, the days to neutrophil and platelet engraftment were similar in these three groups (P = 0.713 and 0.821, respectively). In conclusion, we observed that ID-CY/DOX and LD-CY plus G-CSF for stem cell mobilization resulted in a higher successful rate and higher stem cell yields than G-CSF alone and their engraftment time were similar. Total WBC count >10 × 10(9) /L can be used as a guide to start apheresis in CY-based stem cell mobilization. J. Clin. Apheresis 31:423-428, 2016. © 2015 Wiley Periodicals, Inc.

Inhibitor of Differentiation-1 and Hypoxia-Inducible Factor-1 Mediate Sonic Hedgehog Induction by Amyloid Beta-Peptide in Rat Cortical Neurons.

One major pathological hallmark of Alzheimer's disease (AD) is the accumulation of senile plaques mainly composed of neurotoxic amyloid beta-peptide (Aß) in the patients' brains. Sonic hedgehog (SHH) is a morphogen critically involved in the embryonic development of the central nervous system (CNS). In the present study, we tested whether Aß may induce SHH expression and explored its underlying mechanisms. We found that both Aß25-35 and Aß1-42 enhanced SHH expression in the primary cortical neurons derived from fetal rat brains. Immunohistochemistry revealed heightened expression of SHH in the cortex and hippocampus of aged (9 and 12 months old) AD transgenic mouse brains as compared to age-matched littermate controls. Chromatin immunoprecipitation (ChIP) assay demonstrated that Aß25-35 enhanced binding of hypoxia-inducible factor-1 (HIF-1) to the promoter of the Shh gene in primary cortical cultures; consistently, Aß25-35 induction of SHH was abolished by HIF-1α small interfering RNA (siRNA). Aß25-35 also time-dependently induced inhibitor of differentiation-1 (Id1) that has been shown to stabilize HIF-1α; further, Aß25-35-mediated induction of HIF-1α and SHH was both suppressed by Id1 siRNA. Pharmacological induction of HIF-1α by cobalt chloride and application of the cell-permeable recombinant Id1 proteins were both sufficient to induce SHH expression. Finally, both the SHH pathway inhibitor cyclopamine and its neutralizing antibody attenuated Aß cytotoxicity, albeit to a minor extent. These results thus established a signaling cascade of "Aß â†’ Id1 → HIF-1 → SHH" in primary rat cortical cultures; furthermore, SHH may in part contribute to Aß neurotoxicity.