Synchrony of telomere length among hematopoietic cells.

Objective: Little is known about the relationship of telomere length among leukocyte subsets and cells up the hematopoietic hierarchy. This information is relevant because telomere dynamics in granulocytes were postulated to mirror those of hematopoietic stem cells (HSCs).

Materials And Methods: In newborn umbilical cord blood (UCB), we examined the relationships of telomere length in hematopoietic progenitor cells (HPCs) (CD34(+)CD45(-)) with those in T lymphocytes and granulocytes.

Targeted therapy of human osteosarcoma with 17AAG or rapamycin: characterization of induced apoptosis and inhibition of mTOR and Akt/MAPK/Wnt pathways.

Osteosarcoma is highly resistant to current chemotherapy regimens. Novel therapeutic approaches, potentially involving targeting of specific survival pathways, are needed. We used 17-AAG to inhibit Hsp90 and rapamycin to inhibit mTOR, in the osteosarcoma cell lines, HOS and KHOS/NP.

Protein disulphide isomerase in platelet function.

Platelet protein disulphide isomerase (PDI) has a role in platelet aggregation, probably targeting a thiol-containing platelet surface protein. The thiol-containing P2Y(12) ADP receptor is involved in aggregation induced by most agonists and may be the target of PDI. By excluding the P2Y(12) pathway and using the anti-PDI antibody RL90 this study showed that PDI targets a non-P2Y(12) thiol-protein in aggregation.

Improved mobilization of peripheral blood CD34+ cells and dendritic cells by AMD3100 plus granulocyte-colony-stimulating factor in non-Hodgkin's lymphoma patients.

AMD3100 is a drug capable of mobilizing peripheral blood stem cells (PBSCs) in donors and in cancer patients as a single agent or in combination with granulocyte-colony-stimulating factor (G-CSF). We initiated a phase II study of 11 refractory or relapsed non-Hodgkin's lymphoma (NHL) patients, receiving 16 microg/kg daily of G-CSF for 4 days followed by 240 microg/kg of AMD3100 given subcutaneously on a new schedule of 9-10 h before apheresis collection on day 5. Our aims were to assess the effect of AMD3100 on the mobilization of CD34+ cells, dendritic cells (DCs) and lymphoma cells.

Arsenic trioxide induces p53-dependent apoptotic signals in myeloma cells with SiRNA-silenced p53: MAP kinase pathway is preferentially activated in cells expressing inactivated p53.

Mutations in p53 are the most common genetic abnormality in cancers. Arsenic trioxide (ATO) is an effective chemotherapeutic agent for the treatment of acute promyelocytic leukemia (APL) and is being tested in phase II studies in various types of cancers. We have shown that ATO is a potent inducer of apoptosis in multiple myeloma cells, engaging primarily the intrinsic apoptotic pathway in cells expressing w.