Disease relevance of cytarabine

• Previous studies have demonstrated that 1-beta-D-arabinofuranosylcytosine (ara-C) induces terminal differentiation of human myeloid leukemia cells [1].
• Cellular quantitation of in vivo effects of 1-beta-D-arabinofuranosylcytosine on leukemia L1210 [2].
• Human embryo lung cells were infected with HSV-1 and treated with 1-beta-D-arabinofuranosylcytosine (25 micrograms/ml) for 7 days to minimize both synthesis of virus DNA and infectious virus while allowing expression of early virus genes [3].
• Enhanced metabolism of 1-beta-D-arabinofuranosylcytosine in Down syndrome cells: a contributing factor to the superior event free survival of Down syndrome children with acute myeloid leukemia [4].
• KMOE -2/05 cells, derived from a patient with acute erythremia, became benzidine-positive after the addition of cytosine arabinoside (CA) [5].
• Five patients (16%) experienced serious unexpected neurotoxicity, including seizures, papilledema, cauda equina syndrome (n = 2), and encephalitis after a median of 4 IT administrations of liposomal cytarabine [6].

Psychiatry related information on cytarabine

• Our previous studies with the nucleoside analog 1-beta-D-arabinofuranosylcytosine triphosphate (ara-CTP), a known inhibitor of DNA ligases and polymerases, showed that this agent blocked consolidation of conditioned taste aversion without interfering with short-term memory (STM) [7].

High impact information on cytarabine

• In contrast, 1-beta-D-arabinofuranosylcytosine (araC) and 6-azacytidine (6-aza-CR) did not inhibit DNA methylation or induce muscle formation, whereas 5-6-dihydro-5-azacytidine (dH-aza-CR) was a poor inducer of muscle cells and a poor inhibitor of DNA methylation [8].
• We have previously demonstrated that continuous exposure of human HL-60 human promyelocytes to 1-beta-D-arabinofuranosylcytosine (ara-C) results in the induction of terminal differentiation to monocyte-like cells [9].
• The frequency of chromatid breakage induced by 1-beta-D-arabinofuranosylcytosine was decreased when hamster cell fibroblasts were treated with chemical agents that interferred with DNA synthesis immediately before addition of the analog [10].
• 1-beta-D-arabinofuranosylcytosine-induced chromatid breakage: effect of inhibition of DNA synthesis [10].
• When cells were serum-stimulated in the presence of an inhibitor of DNA synthesis, 1-beta-D-arabinofuranosylcytosine (araC), the levels of hsp70 mRNA were induced to only 20% of the maximal level detected in the absence of the inhibitor [11].

Chemical compound and disease context of cytarabine

• Schedule optimization of hydroxyurea and 1-beta-D-arabinofuranosylcytosine in sarcoma 180 in vitro [12].
• The phosphorylation of 1-beta-D-arabinofuranosylcytosine (ara-C) and 5-azacytidine (5-aza-C) by A(T1)C1-3 hamster fibrosarcoma cells and L5178Y murine leukemic cells was studied, using intact cells [13].
• Thus, in the presence of comparable levels of histidinol, the toxicities of the proliferation-dependent anticancer drugs 1-beta-D-arabinofuranosylcytosine and 5-fluorouracil are eliminated for a variety of normal cell lines but significantly increased for a number of tumorigenic lines [14].
• We have established a human myelogenous leukemia cell line (HL60/AD) that is 10-fold cross-resistant to both 1-beta-D-arabinofuranosylcytosine (ara-C) and daunorubicin; the cell line was isolated from HL60 by simultaneous treatment with these two agents at low drug concentrations attainable in clinical trials [15].
• Thymidine as a kinetic and biochemical modulator of 1-beta-D-arabinofuranosylcytosine in human acute nonlymphocytic leukemia [16].

Biological context of cytarabine

• The resulting DNA/BrdUrd sequences show the kinetics of recovery from araC and allow discrimination of the araC sterilized cells [17].
• Activation of the CPP32 protease in apoptosis induced by 1-beta-D-arabinofuranosylcytosine and other DNA-damaging agents [18].
• Treatment of human myeloid leukemia cells with 1-beta-D-arabinofuranosylcytosine (ara-C) is associated with induction of protein kinase activity and early-response gene expression [19].
• In AML patients treated with anthracyclines and 1-beta-D-arabinofuranosylcytosine, no relation was found between DNA repair capacity and treatment outcome [20].
• The intracellular concentration of 1-beta-D-arabinofuranosylcytosine (ara-C) for half-maximal phosphorylation by leukemic blasts obtained directly from patients was 2.1 +/- 2.5 microM (median, 1.3 microM, N = 25), and the rate of ara-C accumulation actually declined at concentrations above 20 microM in 35% of these cell populations [21].

Anatomical context of cytarabine

• Bivariate DNA/BrdUrd distributions were also applied in the analysis of the response of C3H murine bone marrow cells to treatment in vivo with 1-beta-D-arabinofuranosylcytosine (araC) [17].
• Synergistic interaction between 1-beta-D-arabinofuranosylcytosine, thymidine, and hydroxyurea against human B cells and leukemic blasts in vitro [22].
• Fragments of the ventral half of the spinal cord are incubated for 24 hr in the presence of 10 microM 1-beta-D-arabinofuranosylcytosine in order to eliminate dividing cells and are subsequently dissociated into a suspension of single cells [23].
• Cell line 56-42 was slightly cross-resistant to the ribo-analog 5-azacytidine, but was sensitive to the nucleoside analog 1-beta-D-arabinofuranosylcytosine and to colcemid [24].
• This PALA concentration and exposure interval was associated with a greater than 2-fold increase in both the 45-min generation and 4-hr retention of 1-beta-D-arabinofuranosylcytosine 5'-triphosphate compared to untreated control HL-60 cells [25].

Associations of cytarabine with other chemical compounds

• In rats treated with the S phase-specific chemotherapeutic agent 1-beta-D-arabinofuranosylcytosine, the simultaneous administration of alpha-difluoromethylornithine prevented the recovery of the bone marrow [26].
• Treatment of the cells with 1-beta-D-arabinofuranosylcytosine, 2'-deoxycytidine, calcium ionophore, heat shock, cold shock, or sodium butyrate did not result in increases in the levels of Igf 2 expression [27].
• 1-beta-D-Arabinofuranosylcytosine-5'-stearylphosphate (cytarabine ocfosfate, stearyl-ara-CMP) is a newly synthesized 5'-alkylphosphate derivative of 1-beta-D-arabinofuranosylcytosine (ara-C), which is lipophilic, resistant to inactivation by deamination, and orally active [28].
• The present studies were undertaken to compare anemia-induced erythropoietic responses in femoral marrows and spleens of mice pretreated with Adriamycin (ADR) or 1-beta-D-arabinofuranosylcytosine with those of untreated age-matched controls [29].
• Kinetics and mechanism of the 1-beta-D-arabinofuranosylcytosine-induced potentiation of cis-diamminedichloroplatinum(II) cytotoxicity [30].
• In human AML lines, SCH 900776 not only disrupted cytarabine-induced Chk1 activation and S-phase arrest but also markedly increased cytarabine-induced apoptosis [31].

Gene context of cytarabine

• An MCL1-overexpressing Burkitt lymphoma subline exhibits enhanced survival on exposure to serum deprivation, topoisomerase inhibitors, or staurosporine but remains sensitive to 1-beta-D-arabinofuranosylcytosine [32].
• The present studies demonstrate that PKCdelta is required in part for induction of the stress-activated protein kinase (SAPK/JNK) in cells treated with 1-beta-d-arabinofuranosylcytosine (araC) and other genotoxic agents [33].
• In concert with these results, MUC1 attenuated (i) the loss of mitochondrial transmembrane potential, (ii) mitochondrial cytochrome c release, (iii) activation of caspase-9, and (iv) induction of apoptosis by the antimetabolite, 1-beta-d-arabinofuranosylcytosine [34].
• Distinct functions for WRN and TP53 in a shared pathway of cellular response to 1-beta-D-arabinofuranosylcytosine and bleomycin [35].
• Evidence for involvement of mitogen-activated protein kinase, rather than stress-activated protein kinase, in potentiation of 1-beta-D-arabinofuranosylcytosine-induced apoptosis by interruption of protein kinase C signaling [36].

Analytical, diagnostic and therapeutic context of cytarabine

• Bivariate distributions were measured for bone marrow cells taken from mice that were pulse labeled with BrdUrd at various times after treatment with araC [17].
• Radioimmunoassays using antihuman hemoglobin antibodies revealed an elevated amount of hemoglobin in the CA-exposed cells over that in the control cells (without CA) [5].
• This study establishes the feasibility of an in vitro chemotherapy sensitivity testing of leukemic clonogenic cells by continuous in vitro drug exposure and suggests that the continuous exposure method may be better than the pulse method for antimetabolites such as 1-beta-D-arabinofuranosylcytosine [37].
• The intracellular concentration of 1-beta-D-arabinofuranosylcytosine 5'-triphosphate was assayed by high-performance liquid chromatography [38].
• Therapeutic activity of a thioether-lipid conjugate of 1-beta-D-arabinofuranosylcytosine in human colorectal cancer xenografts [39].

References