Arsenic trioxide as a treatment for myelodysplastic syndrome.

Department of Hematology and Medical Oncology, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Current Hematologic Malignancy Reports 03/2006; 1(1):34-8. DOI: 10.1007/s11899-006-0015-6
Source: PubMed

ABSTRACT Myelodysplastic syndrome (MDS) is a heterogeneous bone marrow disorder primarily affecting older adults, for whom the only curative therapy, bone marrow transplantation, is rarely an option. New therapies, or novel applications of historical therapies, are desperately needed. Arsenic trioxide (ATO), which acts through proapoptotic, antiproliferative, and antiangiogenesis mechanisms, has been used successfully to treat a variety of hematologic malignancies, including MDS. As monotherapy or in combination with other agents, it can effect hematologic improvement in 22% to 26% of patients, with tolerable side effects. MDS patients whose cells express the EVI1 mutation in particular may derive benefit from this therapy.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: This work presents a compartmental model for delivery of three drugs (isoflurane, dopamine and sodium nitroprusside) for regulation of anesthesia. The key feature of this model is that mean arterial pressure, cardiac output and unconsciousness of the patient can be simultaneously regulated. This model is ‘validated’ by carrying out a number of dynamic state simulations and then used for designing model based parametric controllers.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Arsenic is a toxic element and has been responsible for many accidental, occupational, deliberate, and therapeutic poisonings since its discovery in 1250. It occurs in natural waters as the arsenite (As3+) and arsenate (As5+) ions. The solubility of arsenite and arsenate compounds is relatively high so that these ions are readily transported through aqueous routes into the environment. Arsenic can be transferred from soils to crops and accumulates in various food crops and aquatic plants. The fascinating chemistry and toxicity potential make arsenic and its compounds of particular scientific interest and environmental concern. The conventional removal of heavy metals from wastewater, natural waters, and drinking water has only limited effects on arsenic removal. In this review, the main engineering and medical applications, salient health and environmental concerns, novel research on treatment for arsenic poisoning, and removal technologies for arsenic and their derivatives are discussed and enumerated with a view to pursue valuable applied research in order to protect the environment from arsenic toxicity.
    Critical Reviews in Environmental Science and Technology 01/2011; 41(5). · 3.24 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Two myelodysplastic syndrome (MDS) celllines, MUTZ-1 and SKM-1 cells, were used to study the effect of arsenic trioxide (As2O3) on hematological malignant cells. As2O3 induced this two cell lines apoptosis via activation of caspase-3/8 and cleavage of poly (ADP-ribose) polymerase (PARP), a DNA repair enzyme. As2O3 reduced NF-κB activity, which was important for inducing MUTZ-1 and SKM-1 cells apoptosis. As2O3 also inhibited the activities of hTERT in MUTZ-1 and SKM-1 cells. Moreover, the NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC), had no effect on caspase-8 activation, although PDTC did inhibit MUTZ-1 and SKM-1 cells proliferation. Incubation of MUTZ-1 cells with a caspase-8 inhibitor failed to block As2O3-induced inhibition of NF-κB activity. Our findings suggest that As2O3 may induce apoptosis in MUTZ-1 and SKM-1 cells by two independent pathways: first, by activation of caspase-3/8 and PARP; and second, by inhibition of NF-κB activity, which results in downregulation of hTERT expression. We conclude that hTERT and NF-κB are important molecular targets in As2O3-induced apoptosis.
    PLoS ONE 11/2014; 9(11):e113199. · 3.53 Impact Factor