Specific inhibition of the P42/44 mitogen activated protein (map

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...

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514619, A01N 4302, A61K 31335

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active

061471070

ABSTRACT:
Mammaliam cancer cells are effectively killed when treated with a lethal agent (e.g. radiation or chemotherapeutic agents) in combination with an inhibitor specific for the p42/44 MAP kinase cascade "proper".

REFERENCES:
Jarvis et al. "Evidence for Involvement of Mitogen Activated Protein Kinase, Rather than Stress Activated Protein Kinase, in Potentiation of 1-.alpha.-D-Arabinofuransylcytosine-induced apoptosis by Interruption of Protein Kinase C signalling" Molecular Pharmacology54:844-856 (1998).
Wang et al., "Bryostatin 1 enchances paclitaxel-induced mitochondrial dysfunction and apoptosis in human leukemia cells (U937) ectopically expressing Bcl-XI" Leukemia13:1564-1573 (1999).
Kavanaugh et al., "Calcium Dependent Stimulation of Mitogen Activated Protein Kinase Activity in A431 Cells by Low Doses of Ionizing Radiation" Radiation Research 149:579-587 (1998).
Favata, M. F., et al., "Identification of a Novel Inhibitor of Mitogen- activated Protein Kinase Kinase", The Journal of Biological Chemistry, vol. 273, No. 29, Issue of Jul. 17, pp. 18623-18632, 1998.
Dent, P., et al., Review: "The roles of signaling by the p24/44 mitogen- activated protein(MAP) kinase pathway", Leukemia (1998) 12.
Carter, S. et al., "Inhibition of the mitogen activated protein (MAP) kinase cascade potentiates cell killing low dose ionizing radiation in A432 human squamous carcinoma cells", Oncogene (1998) 15.
Alessi, et al., "PD 098059 Is a Specific Inhibitor of the Activation of Mitogen-activated Portein Kinase Kinase in Vitro and in Vivo", vol. 270, No. 46, Issue of Nov. 17, 1995, pp. 27489-27494.

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