Leukemia, cells

Diastovaricias I (70) and II (71) are produced by Streptomyces diastochromogenes. Diastovaricias I and II are active against Friend mouse leukemia cells. Spectral data were used to determine the stmctures (226). 

The mechanism of inhibition has not been characterized, but it is probably related to the ionophoretic properties of these antibiotics. Monensin has been shown to inhibit the intracellular transport of viral membrane proteins of cells infected with Semliki Forest vims (169). The formation of syncytia, normally observed when T-lymphoblastoid cell line (CEM) cells are cocultivated with human immunodeficiency vims (HlV-l)-infected T-ceU leukemia cell line (MOLT-3) cells, was significantly inhibited in the presence of monensin (170). This observation suggests that the viral glycoproteins in the treated cells were not transported to the cell surface from the Golgi membrane. 

Leptosins D-F (258a-c, Scheme 39) [94JCS(P1)1859] were isolated by Takahashi and co-workers from the culture of a strain of Leptosphaeria sp. as cytotoxic substances against the P388 lymphocytic leukemia cell line comparable to that of mitomycin C. Utilizing the nucleophilic substitution reaction of 1-hydroxytryptamines, a simple methodology for the synthesis of core structures of leptosins has been developed (2000H1255). 

Agents which enhance the host s response against neoplasias or force them to differentiate are termed biological response modifiers. Examples include interleukin 2 which is used to treat renal cell carcinoma, interferon a which is active against hematologic neoplasias, and tretinoin (all-trans retinoic acid) which is a powerful inducer of differentiation in certain leukemia cells by acting on retinoid receptors. Side effects include influenza like symptoms, changes in blood pressure and edema. 

Antineoplastic agents that cannot be grouped under subheadings 1-9 include miltefosine which is an alkylphosphocholine that is used to treat skin metastasis of breast cancer, and crispantase which breaks down asparagine to aspartic acid and ammonia. It is active against tumor cells that lack the enzyme asparaginase, such as acute lymphoblastic leukemia cells. Side effects include irritation of the skin in the case of miltefosine and anaphylactic reactions in the case of crispantase. Another recent development is the proteasome inhibitor bortezomib which is used to treat multiple myeloma. 

Table 11 Antitumor activities of organotin(IV) compounds against two types of leukemia cell lines...

Mologni L., Marches E., Nielsen P.E., Gai4BACOrti-Passerini C. Inhibition of promyelocytic leukemia (PML)/retinoic acid receptor-alpha and PML expression in acute promyelocytic leukemia cells by anti-PML peptide nucleic acid. Cancer Res. 2001 61 5468-5473. 

Poly(DL-lactide) was used as the excipient in microspheres of CCNU, a nitrosourea, prepared by a solvent evaporation procedure (96,97). PLA-CCNU microspheres 3.0 pm in diameter were injected i.v. and leukemia cell survival was determined by spleen colony assay. A 100-fold decrease in leukemia cell survival was observed with the microspheres in both spleen and liver compared to untreated controls. Promising results were also obtained with Lewis lung carcinoma in mice. These studies showed that 2- to 4-ym microspheres were preferentially targeted to the lungs. 

A detailed study of the 0-linked oligosaccharides present on the surface of normal granulocytes, chronic myelogenous leukemia cells, and acute myelogenous leukemia cells has been completed. Structures were elucidated by f.a.b.-m.s. after permethylation, and methylation analysis before and after specific exo-glycosidase treatments. Some of the components were shown by f.a.b.-m.s. to be poly(N-acetyllactosaminyl) oligosaccharides, for example, 29. 

SPINOZZI F, PAGLIACCI M C, MIGLIORATI G, MORACA R, GRIGANI F, RICCARDI C, NICOLETTI I (1994) The natural tyrosine kinase inhibitor genistein produces cell cycle arrest and apoptosis in Jurkat T-leukemia cells. LeukRes. 18 431-9. 

HiBASAMi H, ACHiwA Y, FUJIKAWA T and KOMIYA T (1996) Induction of programmed cell death (apoptosis) in human lymphoid leukemia cells by catechin compounds . Anticancer Res, 16, 1943-46. 

Arizti, M.P., Garcia-Orad, A., Sommer, F Silvestro, L, Massiot, P., Chevallier, P., Gutierrez-Zorilla, J.M., Colacio, E., Martinez de Pancorbo, M. andTapiero, H. (1991) Intracellular accumulation and cytotoxic effect of (8-thiotheophyllinate) (triphenylphosphine) gold(l) in Friend leukemia cells. Anticancer Research, 11, 625-628. 

A copper(II) complexes of 5-phenylazo-3-methoxy salicylidene thiosemicarbazone has been shown to have promising growth inhibition activity against P388 lymphocytic leukemia cells sensitive and resistant to adriamycin [196], The complex involves ON coordination of two deprotonated ligands and v(CS) is reported to be unaltered in intensity and position in the complex from its position in the spectrum of the ligand. Inhibition studies with the uncomplexed thiosemicarbazone indicating an important role for the copper(II). 

Once an initial remission is achieved, further intensive therapy is imperative to prevent relapse. Induction therapy fails to provide adequate cell kill, and leukemia cells survive the initial... 

In HSCT, very high doses of chemotherapy with or without total-body radiation (TBI) are given in an attempt to potentiate leukemia cell kill. Hematopoiesis is restored by the infusion of stem cells harvested from an HLA-compatible donor, thereby rescuing the patient from the consequences of total aplasia.13 It is the most effective antileukemic therapy currently available. 

Nishihara H, Maeda M, Oda A, et al. DOCK2 associates with CrkL and regulates Racl in human leukemia cell lines. Blood 2002 100(12) 3968-3974. 

Till KJ, Lin K, Zuzel M, Cawley JC. The chemokine receptor CCR7 and a4 inte-grin are important for migration of chronic lymphocytic leukemia cells into lymph nodes. Neoplasia 2002 99 2977-2984. 

Fluid-phase uptake of macromolecules by cells in general is a slow process, and most administered macromolecules are eliminated from the host before any significant cellular uptake takes place. If, however, the macromolecule contains a moiety that is compatible with a receptor on a specific cell surface, then the macromolecule is attracted to the cell surface and the uptake is enhanced. This maximizes the opportunity for specific-cell capture. This type of cell-specific targeting has been developed to hepatocytes, with galactosamine to T lymphocytes, with anti-T cell antibodies and to mouse leukemia cells, with fucosylamine and other biomolecules. 

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