Cytosine-arabinoside

Chemotherapeutic agents are grouped by cytotoxic mechanism. The alkylating agents, such as cyclophosphamide [50-18-0] and melphalan [148-82-3] interfere with normal cellular activity by alkylation deoxyribonucleic acid (DNA). Antimetabohtes, interfering with complex metaboHc pathways in the cell, include methotrexate [59-05-2] 5-fluorouracil [51-21-8] and cytosine arabinoside hydrochloride [69-74-9]. Antibiotics such as bleomycin [11056-06-7] and doxombicin [23214-92-8] h.a.ve been used, as have the plant alkaloids vincristine [57-22-7] and vinblastine [865-21-4]. 

Chemical Name 4-amino-1(3-D-arabinofuranosyl-2(1H)-pyrimidinone hydrochloride Common Name (3-cytosine arabinoside Structural Formula ... 

Intraperitoneal administration of chemotherapeutic agents has been used for many years as a way of increasing the delivery of drugs to tumors (e.g., ovarian carcinoma) located in the peritoneal cavity (Markman, 1986 Howell and Zimra, 1988). Cisplatin (Casper et al., 1983 Markman et al., 1985), cytosine arabinoside (Ara-C) (King et al., 1984 Markman et al., 1985, 1986), and bleomycin (Markman et al., 1986) are examples of intraperitoneally administered drugs which were already successfully applied in clinical settings. 

Hunt, C. A., Rustum, Y. M., Mayhew, E., and Papahadjopoulos, D. (1979). Retention of cytosine arabinoside in mouse lung following intravenous administration in liposomes of different size, Drug Metabol. Dispos., 7, 124-128. 

Juliano, R. L., and Me Cullough, H. N. (1980). Controlled delivery of an antitumor drug Localized action of liposome encapsulated cytosine arabinoside administered via the respiratory system, J. Pharmacol. Exp. Ther., 214, 381-387. 

King, M. E, Pfeifle, C. E., and Howell, S. B. (1984). Intraperito-neal cytosine arabinoside therapy in ovarian carcinoma, J. Clin. Oncol.. 2, 662-669. 

Mayhew, E., Rustum, Y. M., and Szoka, F. (1982). Therapeutic efficacy of cytosine arabinoside trapped in liposomes, in Targeting of Drugs (G. Gregoriadis, J. Senior, and A. TTOuet, eds.). Plenum Press, New York, pp. 249-260. 

Cylarabine (Ara-C cytosine arabinoside Cytosar U)d ANLL ALL Lymphomatous meningitis NHL MDS High-dose ara-C (HDAC) liposomal cytarabine (Depocyt) for intrathecal use for lymphomatous meningitis... 

Albumin. Albumin is available in highly pure and uniform form, and exhibits low toxicity and good biological stability. It has been used as a carrier for methotrexate and a variety of antiviral drugs [amantadine, fioxuridine (5-fluorodeoxyuridine), and cytar-abine (cytosine arabinoside)] to treat macrophage tumors and infections caused by DNA viruses growing in macrophages. Heavily modified albumins are known... 

As well as NONOates, other NO donors also showed anticancer activity independently. Sodium nitroprusside (SNP), a metal-NO complex, showed cytotoxic effects on the cells of some patients with malignant lymphoma (ML), acute myelocytic leukemia (AML) or chronic myelomonocytic leukemia (CMMoL), but not with multiple myeloma [109]. SNP and cytosine arabinoside (Ara-C) did not share the drug resistance. Interestingly, SNP had no effect on lymphocytes of healthy volunteers. These results suggest that SNP has an anti-tumor effect on human hematological malignant cells. 

G-CSF increases the number of progenitor cells in the bloodstream tenfold. It has been used in the treatment of patients with myelodysplastic syndromes (MDS 8.8) where it can increase neutrophil counts and sometimes improve neutrophil function in these patients. Because some leukaemic cells are able to proliferate rather than differentiate in response to G-CSF, this CSF may potentially induce a leukaemic transformation in these patients however, its combined use with cytotoxic agents such as cytosine arabinoside appears to decrease this possibility. No doubt clinical trials already underway will establish the optimal treatment regimen for G-CSF, so that the beneficial effects of this cytokine for the treatment and management of haematological disorders can be realised. 

There has been some concern expressed regarding the use of CSFs to treat MDS patients. Because these cytokines have proliferative activity, they have the potential to induce a leukaemic transformation in the malignant clone. However, the combined use of CSFs with cytotoxic drugs such as cytosine arabinoside (ara-C) appears promising. If leukaemic clones are induced to proliferate by the cytokine, then they are killed by ara-C as they enter the cell cycle. Other forms of differentiation therapy, such as treatment with retinoids, 1,25-dihydroxyvitamin D3 and interferons, have also been tested, but results have been variable. 

ADCC ADP AM ara-C ATP BAPTA antibody-dependent cellular cytotoxicity adenosine diphosphate acetoxymethyl ester cytosine arabinoside adenosine triphosphate bis- (o-aminophenoxy)-ethane-N,N,N, N -tetraacetic acid... 

Gray LE Jr, Kavlok RJ, Ostby J, et al. 1986. An evaluation of figure-eight maze activity and general behavioral development following prenatal exposure to forty chemicals Effects of cytosine arabinoside, dinocap, nitrofen, and vitamin A. Neurotoxicology 7(2) 449-462. 

Rubas W, et al. Treatment of murine L1210 leukemia and melanoma B16 with lipophilic cytosine arabinoside prodrugs incorporated into unilamellar liposomes. Int J Cancer 1986 37 149. 

Cytosine arabinoside (araC) is used as an effective chemotherapeutic agent for cancer, although resistance to this drug may eventually develop. In certain cases, resistance is related to an increase in the enzyme cytidine deaminase in the tumor cells. This enzyme would inactivate araC to form... 

Laliberte, J., Marquez, V.E. and Momparler, R.L. (1992) Potent inhibitors for the deamination of cytosine arabinoside and 5-aza-2 -deoxycytidine by human cytidine deaminase. 

This enzyme [EC 2.7.1.74] catalyzes the reaction of a nucleoside triphosphate with deoxycytidine to produce a nucleoside diphosphate and dCMP. This enzyme can use any nucleoside triphosphate (except dCTP) as the phosphate-donor substrate and it can phosphorylate cytosine arabinoside as well. 

Cytarabine is an effective antimetabolite in treating leukemia. Like other pyrimidine antimetabolites, cytarabine must be activated by initially transforming into the corresponding nucleotide. The active form of the drag is cytarabine triphosphate. Cytarabine is used for all types of leukemia. Synonyms of this drug are cytosine, arabinoside, and ara-C. 

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