Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human promyelocytic leukemia HL-60 cells provide a useful model system for the study of cell differentiation in vitro. Here the growth of HL-60 cells as a solid clot with fibrin in subrenal capsules (SRC) of mice was studied. The cell volume of HL-60 cells increased 5 and 15-fold between 6-9 days after transplantation into normal and CYT immunosuppressed mice, respectively. Histological study revealed typical proliferation and invasion characteristics of HL-60 cells and higher tumor cell density. RA, RII, Ara-C, Harringtonine and HMBA significantly inhibited the growth of HL-60 cells in SRC of mice. This model provides a useful system for the study of the effect of drugs on cultured tumor cells or leukemia cell lines in vivo.
 ...
PMID:[Inhibitory effects of several antitumor drugs on the growth of HL-60 cells in SRC of mice]. 129 40

Harringtonine, homoharringtonine, deoxyharringtonine and isoharringtonine isolated from Cephalotaxus plant are the esters of cephalotaxine with significant inhibitory activity against P-388 leukemia. In this investigation seventeen new esters of cephalotaxine type alkaloids have been synthesized. Preliminary pharmacological examination showed that compounds 1, 2, 2 + 3, 6 and 8 showed similar antileukemic activity as homoharringtonine. Compounds 4, 5, 15 and 16 showed moderate inhibitory activity. Some structure activity correlations of these esters were discussed.
 ...
PMID:[Studies on the alkaloids of Cephalotaxus. IX. Semi-synthesis of cephalotaxine esters and their anti-leukemic activity]. 141 82

Harringtonine was discovered as an anticancer agent in China. It has been shown to be effective against myeloid leukemia. In this report, we have demonstrated that harringtonine inhibited the growth of human myeloid leukemia cells in vitro at low concentrations. Together with the clinical data in which 28% of the patients could be induced into complete remission only by harringtonine, this agent may be used as a first choice of antileukemia agents in the treatment of myeloid leukemia. The mechanism of the antitumor action of harringtonine is considered to be an effect on protein synthesis and is characterized by breakdown of polysomes to monosomes. The mechanism of action appears to be different from those of the other antileukemia agents, such as cyclophosphamide, daunorubicin, vincristine, or cytosine arabinoside. Harringtonine could be added to the other anti-leukemia agents used routinely in treatment of leukemia, and the combination of harringtonine with the other agents is expected to improve the therapy of myeloid leukemia.
 ...
PMID:[Growth inhibition of human myeloid leukemia cells in vitro by harringtonine]. 230 53

A high-performance liquid chromatographic procedure was developed for the quantitation of homoharringtonine in plasma. Harringtonine was used as an internal standard, and 1 ml of sample was required. The single-step extraction with dichloromethane resulted in almost 100% recovery for homoharringtonine and harringtonine. Analysis was performed on a reversed-phase CN column with amperometric detection. Chromatography was completed in 12 min. At an oxidation potential of +1.0 V, the detection limit was 1 ng/ml at a signal-to-noise ratio of 2. The mean analytical recovery for homoharringtonine was 99.5%. The within-run precision and between-run precision were both less than 11%. The method is equally applicable for plasma or serum, and it has been demonstrated to be applicable for study of the pharmacokinetics of homoharringtonine in patients suffering from acute non-lymphocytic leukaemia.
 ...
PMID:Quantitation of homoharringtonine in plasma by high-performance liquid chromatography with amperometric detection. 259 9

Harringtonine showed cross resistance in adriamycin-resistant murine leukemia P388 (P388/ADM) and human leukemia K562 (K562/ADM) cells. The relative resistance of the P388/ADM and K562/ADM cells to harringtonine was about 7 and 40, respectively. Calcium influx blockers, diltiazem and the biscoclaurine alkaloid cepharanthine enhanced the cytotoxicity of harringtonine in P388/ADM and K562/ADM cells. The extent of enhancement was different for the two drugs, and up to a 9- to 10-fold increase in harringtonine cytotoxicity occurred in P388/ADM cells, and 14- to 22-fold enhancement in K562/ADM cells with diltiazem or cepharanthine. Harringtonine resistance of P388/ADM was circumvented completely, and the resistance of K562/ADM was circumvented partially, by diltiazem or cepharanthine. The mechanism of enhanced cytotoxicity by diltiazem and cepharanthine is probably inhibition of active efflux of harringtonine in P388/ADM and K562/ADM cells.
 ...
PMID:Potentiation of harringtonine cytotoxicity by calcium antagonist diltiazem and biscoclaurine alkaloid cepharanthine in adriamycin-resistant P388 murine leukemia and K562 human leukemia cells. 275 76

Small-dose Harringtonine (1-3 mg infused during 4-5 hr) was used as a single agent to treat 10 patients with acute promyelocytic leukemia. Every patient received one to three courses, each lasting 13-81 days (mean 33 days). The interval between courses (i.e., interruptions) was 5-11 days. During treatment, marrow aplasia occurred in one patient and hypoplasia in three. Pancytopenia occurred in all 10 patients. Complete remission was achieved in seven patients (70%) and cytoreduction in two. In vitro studies showed that, although Harringtonine produced a decrease in leukemic cells in all five series of marrow cultures from five patients, there was only one wherein the decrease was accompanied by a simultaneous absolute increase in differentiated myeloid cells. Considerable discrepancy existed between the culture results and clinical responses. These results seem to suggest that the therapeutic effect of Harringtonine on acute promyelocytic leukemia originates chiefly from cytotoxicity.
Leukemia 1988 Jul
PMID:Small-dose Harringtonine induces complete remission in patients with acute promyelocytic leukemia. 316 99

The antitumor activities and the mechanisms of action of harringtonine and homoharringtonine, alkaloids isolated from cephalotaxus hainanensis Li, were compared to those of vincristine. The results obtained were as follows: Harringtonine and homoharringtonine Significantly inhibited the growth of L1210 cells in culture. The IC50 values were similar to that of vincristine. Harringtonine and homoharringtonine had little effects on changes in the DNA histograms of FL cells at any concentrations, which suggesting that these drugs prolong the duration of each phase of the cell cycle evenly. Harringtonine and homoharringtonine had only a minor effect in arresting P388 cells in mitosis. Harringtonine significantly inhibited the DNA synthesis of P388 leukemia cells in culture, while vincristine weakly inhibited RNA and DNA synthesis. The successive treatment with harringtonine and homoharringtonine were as effective as the successive treatment with vincristine against P388 and L1210 leukemia, while both drugs were ineffective against Lewis lung carcinoma.
 ...
PMID:[Antitumor activities and mechanisms of action of harringtonine and homoharringtonine]. 649 98

Harringtonine (HT) is a new antitumor agent reported to be active in patients with leukemia and lymphoma. The interaction of HT with various antitumor agents was studied in vitro using a human acute myelogenous leukemia cell line KG-1. For the analysis of the drug - drug interaction at the cellular level, Steel proposed the concept of an envelope of additivity. Using this concept, the effect of a two drug combination can be classified as supraadditive (enhancement of the effect), non-interactive (additive), subadditive, and protective (antagonistic). Combination of HT and cytosine arabinoside or HT and dexamethasone produced only additive effects. Combination of HT and methotrexate was subadditive. For HT plus adriamycin or HT plus 5-fluorouracil, data points indicated both subadditive and protective interaction. HT plus acivicin or HT plus L-asparaginase combinations were found to be protective of each other. None of the seven agents produced supraadditive interaction. These results may provide the basis for selecting sequential rather than concurrent combinations which include HT for the treatment of leukemia in man.
 ...
PMID:Effects of harringtonine in combination with acivicin, adriamycin, L-asparaginase, cytosine arabinoside, dexamethasone, fluorouracil or methotrexate on human acute myelogenous leukemia cell line KG-1. 659 May 29

A variety of chemical agents have been shown to induce differentiation in in vitro cultured neoplastic cell lines. We noted that blast cells in the peripheral blood of acute nonlymphoid leukemia patients treated with the drug Harringtonine appeared to undergo morphological changes that suggested differentiation. In view of the relatively minimal myelotoxicity of Harringtonine, we hypothesized that harringtonine was acting by differentiation-induction, which concomitantly arrested cell division. We tested this hypothesis using two different experimental approaches. First, the promyelocytic leukemic cell line, HL-60, was cultured with Harringtonine and shown to differentiate into a cell, which, by functional cell surface marker and morphological criteria, closely resembled normal monocytes. Furthermore, these changes were accompanied, and indeed slightly preceded by, loss of proliferative capacity. Second, to prove that the leukemic blasts were the cells undergoing the changes observed in vivo, freshly isolated leukemia cell populations were cultured with Harringtonine, and morphological changes paralleling those seen in the patients were observed. Thus, the antileukemic effect of Harringtonine appeared to be due to diversion of the proliferating blast cells into a differentiation pathway, which, as in normal myeloid cells, resulted in the arrest of proliferation.
 ...
PMID:Leukemic cell differentiation in vivo and in vitro: arrest of proliferation parallels the differentiation induced by the antileukemic drug Harringtonine. 669 41

Harringtonine (HT) and homoharringtonine (HHT) are two alkaloids isolated from the bark of the evergreen tree Cephalotaxus hainanensis Li in the 1970s. They were found to have activity against murine leukemia, Lewis lung carcinoma and B16 melanoma, and used as anti-leukemia drugs clinically. Apoptosis is an active process of programmed cell suicide and now is believed to be an important target for tumor chemotherapy. In this report, the apoptosis inducing effect of HT and HHT in HL-60 cells were observed. The experiments demonstrated that 2 x 10(-7) mol.L-1 of HT and 10(-7) mol.L-1 of HHT could induce apoptosis in HL-60 cells when the cells were exposed to HT and HHT for 4 h. In agarose gel electrophoresis, DNA extracted from HL-60 cells treated with HT and HHT showed a typical internucleosomal DNA degradation, i.e., DNA ladder and parallel morphological changes as nuclear chromosome segmentation and condensation as well as cytoplasma vacuolation. This effect of HT and HHT was shown to appear in a concentration- and time-dependent manner. The efficacy of HT and HHT in inducing apoptosis of HL-60 cells was found to parallel with their cytotoxic activity in HL-60 cells. These results suggest that the mechanism of antitumor action of HT and HHT is related to their apoptosis inducing activity.
 ...
PMID:[Induction of apoptosis by harringtonine and homoharringtonine in HL-60 cells]. 790 May 38


1 2 Next >>