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Z Estrov

Publications and source records attributed to Z Estrov.

169 records · Page 10Linked to original sources
PubMedDate not supplied

The effect of growth hormone and IGF-I on clonogenic growth of hematopoietic cells in leukemic patients during active disease and during remission--a preliminary report.

The number of survivors of childhood leukemia treated with growth hormone for growth retardation is increasing. The debate about the direct or indirect relationship of GH and insulin-like growth factor I (IGF-I) to the occurrence or recurrence of malignancy, especially in the case of GH therapy in patients with leukemia, is still unresolved. We, therefore, studied the effect of GH and IGF-I on bone marrow of patients with acute leukemia (ALL and AML) in diagnosis and recurrence and in chronic leukemia patients (CML) in remission. GH increased blast colony numbers by a mean of 68% and 77% at GH concentrations of 250 and 300 ng/ml, respectively. IGF-I increased blast colony numbers in ALL patients by 50, 93 and 105%, and in AML patients by 33, 58 and 65%, at IGF-I concentrations of 0.05, 0.25 and 0.5 ng/ml, respectively. In 3 CML patients in remission a granulocyte-macrophage colony forming assay did not reveal stimulation of peripheral blood blast colony formation by GH or IGF-I. Our in vitro data (as previously reported) suggest that GH and IGF-I may promote blast cell proliferation, and the supplemental administration of these peptides in leukemia patients in remission must be carefully monitored for early relapse. Additional studies on bone marrow cells of leukemic patients in remission are needed in order to examine the effects of GH and IGF-I on these cells.

Bone Marrow↗
PubMedDate not supplied

WP744, a novel anthracycline with enhanced proapoptotic and antileukemic activity.

BACKGROUND: MDR1 or MRP1 drug resistance mechanisms seriously limit the efficacy of anthracyclines such as doxorubicin, in the treatment of acute myeloid leukemia (AML). Our studies indicated that reducing basicity, increasing steric hindrance at C-4', and/or lipophilicity may help circumvent P-glycoprotein (P-gp)-mediated anthracycline efflux and thus increase drug retention in MDR-positive cells. From a series of 4'-substituted analogs, 4'-O-benzylated doxorubicin (WP744) was selected for a comparison with the classic anthracycline doxorubicin for their cytotoxic and pro-apoptotic properties. WP744 retains cytotoxic activity against P-gp and MRP-positive cells. METHODS AND RESULTS: In three AML cell lines (K562, KBM-3, and OCIM2) WP744 was markedly more potent (IC50 values of 0.18, <0.05, and <0.05 microg/ml, respectively) than doxorubicin (IC50 values of >0.5, 0.07, and 0.09 microg/ml, respectively). Likewise, WP744 inhibited the colony formation by AML-CFU cells from fresh bone marrow of three AML patients more strongly than doxorubicin. Cell growth inhibition by WP744 is accompanied by apoptosis induction as shown by TUNEL assay in OCIM2 cells. WP744-induced apoptosis appears to be mediated by caspase-3 as apoptotic changes were abrogated in the presence of the caspase 3 inhibitor Z-DEVD-FMK. Accordingly, caspase 3 activity was elevated in the lysates from drug-treated cells. WP744 induced also cleavage of apoptotic marker poly(ADP-ribose)polymerase (PARP). Finally, WP744 at 0.05 microM and greater was a potent inducer of apoptosis (by quantitative DNA fragmentation) in cultured human acute lymphoblastic leukemia (ALL) CEM cells, compared to 0.5 microM doxorubicin needed for a similar effect. CONCLUSION: The novel anthracycline WP744 was found to be an antileukemic agent with proapoptotic activity superior to that of doxorubicin.

Adult↗